ONE CATS BATTLE WITH PANCREATIC CANCER

http://catwithcancer.blogspot.com/search/label/curcumin%20dosage%20for%20cats
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Helpful Information to Share

Although Weasel's health hasn't changed, I do have new news to provide based on this past week, which I hope can provide assistance to others.

About 4 days ago, Weasel vomited all of his dinner.  I don't take these matters lightly and thought that I may need to improve upon the treatment I'm providing him with.  I immediately gave him 1 drop of MMS - something I had decided against, which was diluted in 13 drops of water, with 1 drop of the activator.  It may have been coincidence, but shortly after he seemed fine again and ate some food I gave him.  I started looking up MMS a lot more seriously, as this may be a method of treatment that I can't walk away from.  MMS taken directly can have many negative side effects such as nausea.  I can't afford to have Weasel feel anything of the sort as he'll lose trust in his food.  There is however a method to convert MMS into what is called CDS.  CDS is taking the 'gas' vapours from the MMS and the activator, and releasing it into a bottle of water.  That solution when taken, does not have any of the side effects from taking MMS directly.  On top of that, the bad taste is removed.  I watched a YouTube video that explains how this concoction can be made: http://www.youtube.com/watch?v=x5UHdyeNCbI

I've ordered a syringe online and will test out this method in a couple of weeks.  I'm only giving Weasel a drop a day of this solution, which may be ineffective but I don't dare go up to a level that could cause issues.

In my research for treating cancer, I came across two very useful holistic remedies.  One is called European Mistletoe and the other is Curcumin.  European Mistletoe is actually used in conjunction with chemo and radiation therapy for people, as it nullifies the negative side effects.  It's also used for those who wish to take a holistic approach exclusively.  The success of using European Mistletoe for many forms of cancer is incredible!  Unfortunately for Weasel and I, it's pretty much ineffective for pancreatic cancer.  Pets with other forms of cancer such as liver cancer, can do what's called Mistletoe Therapy which involves injections 2-3 times per week.  Your holistic vet can train you in how to administer the injections so that you can do it from home, instead of driving your kitty back and forth all week which is very hard on a pet.  I highly recommend that you take the time to search in Google for 'Mistletoe Therapy' and 'cancer' to read the impressive case studies out there.  Also, please note that although Mistletoe is deadly to cats when eaten, the extract that is injected into them is not and can prove to be quite beneficial.

What I have successfully been able to administer is Curcumin.  It has virtually no taste as long as you don't purchase Turmeric, which I believe is the spice version that contains Curcumin.  The capsules are rather large so I knock out a small amount on a plate that measures about 1/2" in diameter, as you don't want to give a small cat the same dosage as a full grown adult human.  I mix it with a small amount of half and half cream and add chunks of chicken from the roast I make each week.  The chicken seems to grab the milk mix.  I have a very finicky cat so I'm truly blown away that he eats it and am very thankful.  This website goes into further details on dosage amounts: http://margaret.healthblogs.org/2007/10/11/curcumin-for-cats/

Also, here's just one of many sites that talks about how effective Curcumin is in fighting cancer: http://www.naturalnews.com/037879_curcumin_cancer_cells_turmeric.html

In addition to researching these new aids in the fight against cancer, Weasel and I went by the Holistic Vet Clinic in Newmarket and saw our friend Dr. Haghighat.  Dr. Haghighat was very pleased to see Weasel's progress and informed me that he's gained 3 lbs since his last visit.  This is great news!  Dr. Haghighat was very kind and supportive, listening to my concerns and as usual, focused on the positive and how far we've come with such positive results.  It's nice to talk to someone who cares as much as you do about the wellbeing of your pet and has so many positive insights to share or remind others of.  He was also, as usual very helpful with information and with treating Weasel.  Weasel had an acupuncture treatment which harmonized him and made him very relaxed.  I took a photo of him and you can see the small needle near his back end.  Shortly after this picture was taken he stretched his front paws out to get comfortable so he felt pretty darn good which is rare at a vet's office haha. "

HEMANGIOSARCOMA in cats and dogs

http://www.lapoflove.com/diseases/Hemangiosarcoma.pdf
"What is it?
Hemangiosarcoma (HSA) is an aggressive, malignant cancer of blood vessels that
often grows as a mass in the spleen, liver, or heart, but can also be found growing
in other places in the body. Animals usually present to their veterinarian for sudden
collapse due to internal bleeding from the mass. In most cases, by the time the animal
is showing clinical signs, the cancer has spread to other areas of the body, such as the
lungs. Diagnosis of HSA is suggested by chest and abdominal radiographs (x-rays),
abdominal ultrasound and aspiration of abdominal fluid, and biopsy of the mass via
exploratory surgery.
How is it treated?
Unfortunately, while there are treatment options available, there are no cures for this
disease. While surgery may be an effective option for removing the primary tumor
and temporarily stopping bleeding, it is not capable of removing all of the metastatic
disease, which is usually microscopic at the time of diagnosis. Chemotherapy is often
used in conjunction with surgery to help combat the microscopic cancer cells.
What is the prognosis for hemangiosarcoma (HSa)?
A diagnosis of HSA almost always carries a poor prognosis, the only exception being
dermal HSA originating from the skin with no internal involvement. If treatment is
not an option, euthanasia should be considered to prevent suffering from internal
bleeding. Surgery alone to remove the primary tumor carries a median survival time of
1-4 months, while chemotherapy in addition to surgery carries a median survival time
of 6-8 months. Even with surgery and chemotherapy, the disease will progress and the
cancer cells with continue to metastasize, creating masses throughout the entire body.
Hemorrhages may occur from each cancer site, which may cause transient weakness
until the bleeding stops. If the bleeding does not stop, the patient will start to show
signs of shock and collapse. A personalized treatment plan is important to slow the
progression of HSA. Talk to your veterinarian regarding the best\\ treatment protocol
for your pet.
What symptoms can present as the disease progresses?
Early STagES:
x Loss of appetite
x Weight loss
x Lethargy
x Exercise intolerance
x Vomiting/diarrhea
x Pale gums
x Possible distended abdomen
laTE STagES:
x Persistent early stages
x Reclusive behavior
x Distended abdomen
x Dull mentation
x Difficulty breathing
x Panting, gasping for breath
x Possible black, tarry stool
x Sudden collapse
x Unable to rise

http://en.wikipedia.org/wiki/Cancer_in_cats 

Cancer in cats

Could my cat be a blood donor?

http://www.chicagotribune.com/news/local/suburbs/libertyville/community/chi-ugc-article-could-my-cat-be-a-blood-donor-2013-12-06,0,5827046.storyJust like people, sometimes cats are in need of a blood transfusion. Veterinary clinics (especially emergency and specialty clinics) are in need of donors so that they have blood on hand for emergency cases. By checking with your local specialty clinic, you can find out how your pet may help and if there are added benefits for your pet donating.

Why are blood donors needed? 
There are a variety of reasons veterinary clinics need blood for transfusions. Cats that suffer from acute blood loss caused by trauma, internal bleeding or cancer would likely need a transfusion to survive. Blood transfusions are also helpful in cases of anemia (from kidney failure, immune problems or feline leukemia), clotting issues, hemophilia or other health issues

Benefits of donating blood
When your cat donates blood, he or she is saving a life. Specialty clinics also offer incentives to blood donors like examinations, blood work monitoring and heartworm preventative if your pet is able to donate four to six times a year. Feline blood donors are screened for a number of infectious diseases, hemoglobin levels and metabolic screenings at no charge to you.

Who can donate? 
Cats that are good candidates meet the following criteria –

• Healthy and up-to-date on vaccines
• Between 2 to 7 years old
• Has not had a blood transfusion
• Medication free except for heartworm and flea and tick prevention
• At least 10 pounds of lean body weight
• Indoor only
• Feline leukemia and feline immunodeficiency virus (FIV) negative
• Hasn’t been bred "

Comprehensive guide to cancer diagnosis and treatment in cats and dogs

Comprehensive guide to cancer diagnosis & treatment in cats & dogshttp://petcancercenter.org/

Sound-induced seizures in cats

http://www.icatcare.org//surveys
"Witnessing your cat having a seizure is a very upsetting and distressing event. A seizure is a sudden and uncontrolled burst of electrical activity that may cause chomping and chewing, foaming at the mouth, jerking of the legs, and the passing of urine or stools. Cats are usually unresponsive during a seizure and gradually regain normal consciousness thereafter.

Although seizures commonly occur without any obvious trigger, we have found over the years that cats may have seizures in response to particular noises. Some of the sounds that we have known to trigger seizures in cats include the sound of breaking the tin foil from treatment or tablet packaging, the crinkling of tin foil, a metal spoon dropping into a ceramic feeding bowl, a daisy wheel printer (now a thing of the past), a digital alarm, the hammering of a nail, the clicking of an owner’s tongue or even the slapping of an owner’s forehead!

This is not something that is unique to cats. In human patients, the condition where seizures occur in response to a trigger is known as reflex epilepsy. If this trigger is a sound then the term audiogenic reflex epilepsy is used. Little is known about the condition in people or cats. Therefore, with the backing of International Cat Care, Davies Veterinary Specialists are looking to find owners who have cats with suspected noise-induced or audiogenic seizures. The aim is to use this information to help cats and it may even become useful to help people who suffer from this difficult condition.

If you think your cat may have auditory induced reflex seizures, or you would like further information, then please contact Mark Lowrie either by email:mll@vetspecialists.co.uk or telephone 01582 883950."

Fighting Cat Cancer in Smarter Ways

http://www.naturalcatcareblog.com/landing/fighting-cat-cancer/

Fighting Cat Cancer in Smarter Ways
"If your life has been touched by feline cancer, my heart goes out to you—more than you know.

One of my biggest motivations for getting more serious about natural cat care and eventually creating this blog was that I had a feline soul mate diagnosed with high-grade intestinal lymphoma–and I was knocked flat with despair and shock.

How did it happen? Where did I go wrong, and…“what do we do now?”  Should we try chemotherapy, which only promised to extend her life several months, or should we try an alternative?

I was not prepared. And it didn’t go that well. I spent endless hours researching options and trying to save her, but it was all too little, too late.

That’s why a dream for this blog is to give you a place to go if you’ve lost a cat to cancer and want to know how to prevent that from happening again. Or if you have a cat cancer diagnosis and want to get some helpful information.

If you want to make sure your cat never gets cancer

I’m always looking into how prevent cat cancer. Here’s a great starting place:

• Go grain-free, like the foods here, if you want to prevent intestinal cat cancer (it’s a common one). Cats eating grains appear much more likely to quietly develop IBD, which many experts believe is a precursor to the deadly intestinal lymphoma.  (You may be interested in another vet’s post about this on ConsciousCat.net too.)
• See 3 other things I discovered that appear to likely to prevent cancer in cats.

See also Jean Hofve, DVM’s extensive article on preventing cancer in cats.

If your cat has been diagnosed with cancer

Here’s what I have for you so far…

One of the most important things I learned

I want to tell you this right away because I believe it was a factor in our cat not beating cancer.

Most cancer-killing methods, even many alternative ones, will essentially breed stronger cancer cells. That’s because the tiny little cells that survived start growing and breeding, given half a chance. These are the cells that were strong and smart enough to be resistant to the stuff you were using to kill them.

Think of how over-use of antibiotics has spawned stronger, antibiotic-resistant bacteria. It’s the same kind of problem.

This means you must keep up the fight and not ease off until an expert you really trust confirms that every single cancer cell has been totally wiped out. (That’s different from just saying a tumor is gone, by the way.)

So if you are using chemotherapy and your cat isn’t doing well with it, you may need to ease off the chemo but you’ve got to keep going strong then with an alternative that she does tolerate well. One way or another, you need to make sure the cancer is getting constant, even treatment—no letting up too early.

One cat’s success story

See Incurable to Cancer-Free in One Year: How Nate-the-Cat Survived High Grade Lymphoma. This interview made me very happy! My only regret is I didn’t hear about this approach when I needed it."

more at this link

Cancer in Cats (Good article by a Vet)

http://manhattancats.com/Articles/Feline_Cancer.html by

Arnold Plotnick MS, DVM, ACVIM, ABVP
 "“I’m feeling a lump in Annie’s abdomen”. 

As a veterinarian, I’m sometimes forced to give unwelcome news.  I could not have uttered words more devastating, however, than those just delivered to Christoph and Ellen Franzgrote.  A year ago, they watched their cat Mia succumb to lymphosarcoma, a cancer of the lymphoid tissues.  Mia couldn’t abide her chemotherapy and quickly surrendered to the disease at the age of five.  Today’s routine wellness check on Mia’s daughter, Annie, yielded an abdominal mass. 

The prevalence of feline cancer is increasing.  Advances in veterinary medicine have allowed cats to live longer, and cancer is generally a disease of older animals. This is the fateful price cats must pay for living longer.

Cancer is unrestrained cell division and growth.  Normally, cell division is tightly regulated.  When a single cell undergoes a series of genetic mutations, cancer may arise, causing cell division to become unregulated, resulting in a tumor. While the cause of most cancers remains unknown, environmental agents can induce cancerous changes in cells, such as viruses, chemicals, radiation, and some hormones.  The effects of these agents can accumulate over time, explaining why cancer more commonly affects older animals.

Another word for cancer is neoplasia (“new growth”), and tumors are sometimes referred to as neoplasms.  Tumors are classified as benign or malignant.  Benign tumors remain at their original site.  Malignant tumors can invade surrounding tissues and gain access to the bloodstream or lymphatic vessels, and then be transported to nearby lymph nodes or other part(s) of the body.  This is called metastasis, and is commonly how cancer spreads. The word cancer generally implies malignancy.  While benign tumors are generally less worrisome and malignant tumors are more troubling, this distinction isn’t always clear-cut.  A seemingly benign tumor may behave malignant clinically, impinging on nearby structures and becoming impossible to remove or treat. 

Cats are susceptible to a variety of cancers.  Among the most devastating are lymphosarcoma, squamous cell carcinoma, and mammary (breast) cancer.

Lymphosarcoma is a cancer arising from lymphoid tissues involving any organ. Affected cats ranges, on average, from 2 to 6 years, although any age cat is susceptible.  Infection with the feline leukemia virus increases the risk of developing lymphosarcoma.  This is especially true of younger cats.  Older cats that develop lymphoma are less likely to be concurrently infected with the feline leukemia virus.  Lymphosarcoma is often categorized by anatomic location.  The five types are mediastinal (involving structures inside the chest), alimentary (digestive system), multicentric (the lymph nodes), leukemic (the bloodstream), and extranodal (other organs, such as the kidneys, eyes, nervous system, nasal cavity, and skin).  

In cats, the most common sites are the gastrointestinal tract, the mediastinum (structures in the chest such as the thymus and associated lymph nodes), the liver, spleen, and kidneys.    Fortunately, lymphosarcoma is fairly responsive to chemotherapy. 

Squamous cell carcinoma (SCC) accounts for 15% of all feline skin tumors. These tumors usually involve light or unpigmented skin.  Sun exposure increases the risk of developing SCC.  Solar-induced SCC is referred to as “actinic” SCC. The most common locations are the hairless area of the nose, the eyelids, and ears.  Older cats are at higher risk; the mean age for affected cats is 12 years.  Siamese cats, with their pigmented skin, are less likely to develop SCC than other breeds. SCC of the skin is often amenable to treatment.  Dr. Tim Rocha is a board-certified veterinary oncologist in New York City who has had good success treating SCC of the skin.  “Except in advanced cases, we have several therapeutic options that all have good to excellent success rates.  Surgery, radiation therapy, and intralesional chemotherapy (where the drug is injected directly into the tumor) have all been shown effective in treating this cancer”, says Dr. Rocha. SCC may also affect a cat’s mouth. This is often disastrous, as oral SCC is much worse than the skin form. “Unfortunately”, says Dr. Rocha.  “95% of these oral SCC cases are diagnosed only after the cat shows dramatic changes in appearance, such as swelling of the jaw or face, severe weight loss, or blood in the mouth”.  

Treatment for oral SCC is often unrewarding.  “It is sad that we have yet to identify any treatments that are reliably helpful.”  Surgery offers the best chance for survival, but most of the time it has progressed too far. “If a SCC is removed surgically in it’s entirety, a cat may become one of the rare 5% of cats that beat this diagnosis”, says Dr. Rocha.  

Mammary tumors tend to develop in older cats. They account for 17% of neoplasms in female cats.  Spaying dogs before their first heat lessens the risk of future mammary tumor development, and this also holds true for cats. Rarely, male cats will be affected.  In cats, the behavior of mammary tumors is very different compared to dogs.  While roughly half of canine mammary tumors are malignant, at least 80% of feline mammary tumors are malignant. Siamese cats have at least twice the risk of developing mammary tumors compared to other breeds, and they tend to be affected earlier, reaching a plateau at 9 years of age.  More than half of affected cats show multiple gland involvement.  Unfortunately, mammary cancer may spread to the lungs quickly, making the prognosis guarded or poor.  Surgery is the best treatment option for feline mammary tumors. Dr. Kathy Kazmierski, a veterinary oncologist at Garden State Veterinary Specialists in New Jersey, says that the most important prognostic factor for survival is the size of the tumor at diagnosis and removal.  “Tumors that are less than 2 centimeters big are much better than those that are 3 centimeters or greater”, she says.  “Follow-up chemotherapy is often recommended”, says Dr. Kazmierski, “but there are not enough cases studied to know if that offers a true survival benefit”. 

To make a definitive diagnosis of cancer, tests must be performed.  Blood work, x-rays, and ultrasound provide a great deal of information, but ultimately, most cases require a biopsy to confirm the diagnosis."

MORE AT THE LINK ===> http://manhattancats.com/Articles/Feline_Cancer.html

Cancer in Cats: Types, Symptoms, Prevention, and Treatment

http://pets.webmd.com/cats/guide/cancer-in-cats-types-symptoms-prevention-and-treatment

Cancer in Cats: Types, Symptoms, Prevention, and Treatment
"Although cancer isn’t as common in cats as it is in dogs, it still affects a number of our feline friends. And because cats have a tendency to mask illnesses, it can be harder to detect. This often leads to later diagnoses and more difficult and costly treatments. So we talked to Dave Ruslander, a veterinary oncologist and past president of the Veterinary Cancer Society, about feline cancers and the latest treatments for cats diagnosed with the disease.

Q: How common is cancer in cats? What are some of the more common cancers found in cats?

A: Cancer in cats is less common than cancer in dogs. It’s probably half the rate that we see in dogs. But when we see cancer in cats, it tends to be a more aggressive form.

One of the most common cancers we see in cats is lymphoma, which is associated with the feline leukemia virus (FeLV). Even though there’s a vaccine for feline leukemia now, we still see a number of cats that have been exposed to it, and exposure greatly increases a cat’s chance of developing feline lymphoma.

We also see oral squamous carcinoma, similar to what people get. We see a tumorcalled fibrosarcoma, or soft tissue sarcoma, which is a tumor developing in muscle or in the connective tissue of the body. That’s the one associated with injections and vaccinations, which some people call injection-site sarcoma.

We see other kinds of tumors as well, but they are much less common -- lung tumors, brain tumors, nasal tumors, liver tumors. We don’t see as many mammary tumors these days because so many people have their cats spayed now. So all of those are just a smattering here and there.

Q: What are some of the symptoms of feline cancers?

A: Cats are tricky because they hide disease well. Externally we can see lumpsand bumps. Vomiting and diarrhea are common signs of gastrointestinal lymphoma. Difficulty in breathing can be a sign, because some cancers can cause fluid in the lungs.

Sometimes it’s just a refusal to eat and weight loss, a rough coat, or just generally what we call a failure to thrive. It’s always best, if your cat is acting ill or lethargic for any period of time, to take it to your veterinarian to be checked out.

Q: Is it difficult to diagnose the type of cancer a cat has contracted?

A: With a biopsy the pathologist can usually tell us the type of cancer. But sometimes it’s not so clear. And sometimes people are reluctant to go forward without a firm prognosis. Often we can’t go forward until we know what the actual subtype is. It can take some special testing or some special stains for us to delineate the type of cancer, and sometimes people just aren’t willing to do that."

SEE MORE AT THE LINK SOURCE

Understanding the Immune System - ARTICLE : The Adaptive Immune Systemn

http://faculty.ccbcmd.edu/courses/bio141/lecguide/unit5/cellular/cmidefense
/cytokines/cytokines.html THE ADAPTIVE IMMUNE SYSTEM
"III. CELL-MEDIATED IMMUNITY

A. Ways That Cell-Mediated Immunity Helps to Defend the Body

3. Stimulating Cells to Secrete Cytokines

The overall purpose of this Learning Object is to introduce how cytokines function to regulate innate and adaptive immune defenses.

LEARNING OBJECTIVES FOR THIS SECTION

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Adaptive (acquired) immunity refers to antigen-specific defense mechanisms that take several days to become protective and are designed to remove a specific antigen (def). This is the immunity one develops throughout life. There are two major branches of the adaptive immune responses: humoral immunity and cell-mediated immunity.

1. humoral immunity (def): humoral immunity involves the production of antibody molecules in response to an antigen (def) and is mediated by B-lymphocytes.
2. cell-mediated immunity (def): Cell-mediated immunity involves the production of cytotoxic T-lymphocytes, activated macrophages, activated NK cells, and cytokines in response to an antigen (def) and is mediated by T-lymphocytes.
Cell-mediated immunity (CMI) is an immune response that does not involve antibodies but rather involves the activation of macrophages and NK-cells, the production of antigen-specific cytotoxic T-lymphocytes (def), and the release of various cytokines (def) in response to an antigen (def). Cellular immunity protects the body by:

1. activating antigen-specific cytotoxic T-lymphocytes (CTLs) that are able to lyse body cells displaying epitopes of foreign antigen on their surface, such as virus-infected cells, cells with intracellular bacteria, and cancer cells displaying tumor antigens;
2. activating macrophages and NK cells, enabling them to destroy intracellular pathogens; and
3. stimulating cells to secrete a variety of cytokines that influence the function of other cells involved in adaptive immune responses and innate immune responses.

Cell-mediated immunity is directed primarily microbes that survive in phagocytes and microbes that infect non-phagocytic cells. It is most effective in destroying virus-infected cells, intracellular bacteria, and cancers. It also plays a major role in delayed transplant rejection.

In this section we will look at how cell-mediated immunity helps to defend the body by stimulating cells to produce and secrete a variety of cytokines.

---

3. Stimulating Cells to Secrete a variety of Cytokines that Influence the Function of Other Cells Involved in Adaptive Immune Responses and Innate Immune Responses
Cytokines (def) are low molecular weight, soluble proteins that are produced in response to an antigen and function as chemical messengers for regulating the innate and adaptive immune systems. They are produced by virtually all cells involved in innate and adaptive immunity, but especially by T helper (T_H) lymphocytes. The activation of cytokine-producing cells triggers them to synthesize and secrete their cytokines. The cytokines, in turn, are then able to bind to specific cytokine receptors on other cells of the immune system and influence their activity in some manner.
Cytokines are pleiotropic, redundant, and multifunctional.

• Pleiotropic means that a particular cytokine can act on a number of different types of cells rather than a single cell type.
• Redundant refers to to the ability of a number of different cytokines to carry out the same function.
• Multifunctional means the same cytokine is able to regulate a number of different functions.

Some cytokines are antagonistic in that one cytokine stimulates a particular defense function while another cytokine inhibits that function. Other cytokines are synergistic wherein two different cytokines have a greater effect in combination than either of the two would by themselves.
There are three functional categories of cytokines:

1. cytokines that regulate innate immune responses,
2. cytokines that regulate adaptive Immune responses, and
3. cytokines that stimulate hematopoiesis (def).

a. Cytokines that regulate innate immunity are produced primarily by mononuclear phagocytes such as macrophages (def) and dendritic cells (def), although they can also be produced by T-lymphocytes (def), NK cells (def), endothelial cells (def), and mucosal epithelial cells. They are produced primarily in response to pathogen-associated molecular patterns (PAMPs) such as LPS, peptidoglycan monomers, teichoic acids, unmethylated cytosine-guanine dinucleotide or CpG sequences in bacterial and viral genomes, and double-stranded viral RNA. Cytokines produced in response to PRRs on cell surfaces, such as the inflammatory cytokines IL-1, IL-6, IL-8, and TNF-alpha, mainly act on leukocytes and the endothelial cells that form blood vessels in order to promote and control early inflammatory responses (see Fig. 1). Cytokines produced in response to PRRs that recognize viral nucleic acids, such as type I interferons, primarily block viral replication within infected host cells (see Fig. 2 and Fig. 3).
Examples include:

1. Tumor necrosis factor-alpha (TNF-alpha)
TNF-alpha is the principle cytokine that mediates acute inflammation. In excessive amounts it also is the principal cause of systemic complications such as the shock cascade. Functions include acting on endothelial cells (def) to stimulate inflammation (def) and the coagulation pathway; stimulating endothelial cells to produce selectins and ligands for leukocyte integrins (see Fig. 1) during diapedesis (def); stimulating endothelial cells and macrophages to produce chemokines (def) that contribute to diapedesis, chemotaxis (def), and the recruitment of leukocytes; stimulating macrophages to secrete interleukin-1 (IL-1) for redundancy; activating neutrophils(def) and promoting extracellular killing by neutrophils; stimulating the liver to produce acute phase proteins (def), and acting on muscles and fat to stimulate catabolism for energy conversion. In addition, TNF is cytotoxic for some tumor cells; interacts with the hypothalamus to induce fever and sleep; stimulates the synthesis of collagen and collagenase for scar tissue formation; and activates macrophages. TNF is produced by monocytes,macrophages, dendritic cells, T_h1 cells, and other cells.
2. Interleukin-1 (IL-1)
IL-1 function similarly to TNF in that it mediates acute inflammatory responses. It also works synergistically with TNF to enhance inflammation. Functions of IL-1 include promoting inflammation (def); activating the coagulation pathway, stimulating the liver to produce acute phase proteins (def), catabolism of fat for energy conversion, inducing fever and sleep; stimulates the synthesis of collagen and collagenase for scar tissue formation; stimulates the synthesis of adhesion factors on endothelial cells and leukocytes (see Fig. 1) for diapedesis (def); and activates macrophages. IL-1 is produced primarily by monocytes, macrophages, dendritic cells, endothelial cells, and some epithelial cell.
3. Chemokines (def)
Chemokines are a group of cytokines that enable the migration of leukocytes from the blood to the tissues at the site of inflammation. They increase the affinity of integrins on leukocytes for ligands on the vascular wall (see Fig. 1 during diapedesis (def) , regulate the polymerization and depolymerization of actin in leukocytes for movement and migration, and function as chemoattractants (def) for leukocytes. In addition, they trigger some WBCs to release their killing agents for extracellular killing and induce some WBCs to ingest the remains of damaged tissue. Chemokines also regulate the movement of B-lymphocytes (def), T-lymphocytes (def), and dendritic cells (def) through the lymph nodes and the spleen. When produced in excess amounts, chemokines can lead to damage of healthy tissue as seen in such disorders as rheumatoid arthritis, pneumonia, asthma, adult respiratory distress syndrome (ARDS), and septic shock. Examples of chemokines include IL-8, MIP-1a, MIP-1b, MCP-1, MCP-2, MCP-3, GRO-a, GRO-b, GRO-g, RANTES, and eotaxin. Chemokines are produced by many cells including leukocytes, endothelial cells, epithelial cells, and fibroblasts.
4. Interleukin-12 (IL-12)
IL-12 is a primary mediator of early innate immune responses to intracellular microbes. It is also an inducer of cell-mediated immunity. It functions to stimulate the synthesis of interferon-gamma by T-lymphocytes (def) and NK cells (def); increases the killing activity of cytotoxic T-lymphocytes (def) and NK cells; and stimulates the differentiation of naive T4-lymphocytes (def) into interferon-gamma producing T_h1 cells. It is produced mainly by macrophages and dendritic cells.
5. Type I Interferons (def)
Interferons modulate the activity of virtually every component of the immune system. Type I interferons include 13 subtypes of interferon-alpha, interferon-beta, interferon omega, interferon-kappa, and interferon tau. (There is only one type II interferon, interferon-gamma, which is involved in the inflammatory response.)
The most powerful stimulus for type I interferons is the binding of viral DNA or RNA to toll-like receptors (def) TLR-3, TLR-7, and TLR-9 in endosomal membranes (def).

a. TLR-3 - binds double-stranded viral RNA;
b. TLR-7 - binds single-stranded viral RNA, such as in HIV, rich in guanine/uracil nucleotide pairs;
c. TLR-9 - binds unmethylated cytosine-guanine dinucleotide sequences (CpG DNA) found in bacterial and viral genomes but uncommom or masked in human DNA and RNA.

Flash animation showing toll-like receptors (TLRs) recognizing viral double-stranded RNA.

html5 version of animation for iPad showing toll-like receptors (TLRs) recognizing viral double-stranded RNA.

Signaling pattern recognition receptors located in the cytoplasm of cells such as RIG-1 and MDA-5 also signal synthesis and secretion of type-I interferons.

For More Information: Pathogen-Associated Molecular Patterns (PAMPs) from Unit 4

For More Information: Pattern-Recognition Receptors from Unit 4

Type I interferons, produced by virtually any virus-infected cell, provides an early innate immune response against viruses. Interferons induce uninfected cells to produce enzymes capable of degrading mRNA. These enzymes remain inactive until the uninfected cell becomes infected with a virus. At this point, the enzymes are activated and begin to degrade both viral and cellular mRNA. This not only blocks viral protein synthesis, it also eventually kills the infected cell (see Fig. 2 andFig. 3). In addition, type I interferons also cause infected cells to produce enzymes that interfere with transcription of viral RNA or DNA. They also promote body defenses by enhancing the activities of CTLs, macrophages, dendritic cells, NK cells, and antibody-producing cells.

GIF animation showing the antiviral nature of interferon.

Type I interferons also induce MHC-I antigen expression needed for recognition of antigens by cytotoxic T-lymphocytes (def); augment macrophage (def), NK cell (def), cytotoxic T-lymphocytes, and B-lymphocyte (def) activity; and induce fever. Interferon-alpha is produced by T-lymphocytes (def), B-lymphocytes, NK cells, monocytes/macrophages; interferon-beta by virus-infected cells, fibroblasts, macrophages, epithelial cells, and endothelial cells.
6. Interleukin-6 (IL-6)
IL-6 functions to stimulate the liver to produce acute phase proteins (def); stimulates the proliferation of B-lymphocytes (def); and increases neutrophil (def)production. IL-6 is produced by many cells including T-lymphocytes, macrophages, monocytes, endothelial cells, and fibroblasts.
7. Interleukin-10 (IL-10)
IL-10 is an inhibitor of activated macrophages and dendritic cells and as such, regulates innate immunity and cell-mediated immunity. IL-10 inhibits their production of IL-12, co-stimulator molecules, and MHC-II molecules (def), all of which are needed for cell-mediated immunity (def). IL-10 is produced mainly by macrophages, and T_H2 cells.
8. Interleukin 15 (IL-15)
IL-15 stimulates NK cell (def) proliferation and proliferation of memory T8-lymphocytes (def). IL-15 is produced by various cells including macrophages.
9. Interleukin-18 (IL-18)
IL-18 stimulates the production of interferon-gamma by NK cells (def) and T-lymphocytes (def) and thus induces cell-mediated immunity (def). It is produced mainly by macrophages.

b. Cytokines that Regulate Adaptive Immune Responses (Humoral Immunity and Cell-Mediated Immunity)

Cytokines that regulate adaptive immunity are produced primarily by T-lymphocytes that have recognized an antigen specific for that cell. These cytokines function in the proliferation and differentiation of B-lymphocytes and T-lymphocytes after antigen recognition and in the activation of effector cells.
Examples include:

1. Interleukin-2 (IL-2)
IL-2 is a growth factor for NK cells and antigen-stimulated T-lymphocytes and B-lymphocytes. IL-2 also increases the killing ability of NK cells; increases the synthesis of other cytokines; increases Fas-mediated apoptosis; and stimulates antibody synthesis by B-lymphocytes. IL-2 is produced mainly by T4-lymphocytes and to a lesser extent T8-lymphocytes.
2. Interleukin-4 (IL-4)
IL-4 is a major stimulus for production of IgE and the development of T_h2 cells for defense against helminths and arthropods. It also antagoizes the effects of interferon-gamma and thus inhibits cell-mediated immunity. IL-4 is produced mainly by T_H2 cells and mast cells.
3. Interleukin-5 (IL-5)
IL-5 is a growth and activating factor for eosinophils as a defense against helminths and arthropods. It also stimulates the proliferation and differentiation of antigen-activated B-lymphocytes and the production of IgA. IL-5 is produced mainly by T_H2 cells.
4. Interferon-gamma (IFN-gamma)
Interferons modulate the activity of virtually every component of the immune system. Type I interferons include more than 20 types of interferon-alpha, interferon-beta, interferon omega, and interferon tau. There is only one type II interferon, interferon-gamma. Type II interferon is produced by activated T-lymphocytes as part of an immune response and functions mainly to promote the activity of the components of the cell-mediated immune system such as CTLs, macrophages, and NK cells.
IFN-gamma is the principal cytokine for activating macrophages. It also induces the production of MHC-I molecules, MHC-II molecules, and co-stimulatory molecules by APCs in order to promote cell-mediated immunity and activates and increases the antimicrobial and tumoricidal activity of monocytes, macrophages, neutrophils, and NK cells. IFN-gamma stimulates the differentiation of T4-lymphocytes into T_H1 cells and inhibits the proliferation of T_H2 cells; stimulates the production of IgG subclasses that activate the complement pathway and promote opsonization; and augments or inhibits other cytokine activities. IFN-gamma is produced primarily by T_H1 cells, CD8⁺ cells, and NK cells.
5. Transforming growth factor-beta (TGF-beta)
TGF-beta functions to inhibit the proliferation and effector function of T-lymphocytes; inhibit the proliferation of B-lymphocytes; and inhibits macrophage function. It also promotes tissue repair. TGF-beta is produced by T-lymphocytes, macrophages, and other cells.
6. Lymphotoxin (LT)
LT plays a role in the recruitment and activation of neutrophils and in lymphoid organogenesis. Being chemically similar to TNF, LT is also a mediator of acute inflammatory responses. LT is made by T-lymphocytes.
7. Interleukin-13 (IL-13)
IL-13 increases the production of IgE by B-lymphocytes, inhibits macrophages, and increases mucus production. IL-13 is made primarily by T_H2 cells.

c. Cytokines that Stimulate Hematopoiesis

Produced by bone marrow stromal cells, these cytokines stimulate the growth and differentiation of immature leukocytes.
Examples include:

1. Colony-stimulating factors (CSF)
Promote the production of colonies of the different leukocytes in the bone marrow and enhance their activity. Examples include granulocyte macrophage colony stimulating factor (GM-CSF), granulocyte colony stimulating factor (G-CSF), and macrophage colony stimulating factor (M-CSF). In addition to their role in promoting production of leukocyte colonies, the CSFs also appear to promote their function. For example, when GM-CSF binds to receptors on neutrophils, eosinophils, and monocytes, it activates these cells and inhibits their apoptosis. GM-CSF increases adhesion of these cells to capillary walls during diapedesis, enhances their phagocytosis and extracellular killing, and increases both superoxide anion generation and antibody-dependent cytotoxicity. The various CSFs are produced by T-lymphocytes, macrophages, and other cells.
2. Stem cell factor
Stem cell factor makes stem cells in the bone marrow mor responsive to the various CSFs. It is made mainly by bone marrow stromal cells.
3. Interleukin-3 (IL-3)
IL-3 supports the growth of multilineage bone marrow stem cells. IL-3 is made primarily by T-lymphocytes.
4. Interleukin-7 (IL-7)
IL-7 plays a role in the survival and proliferation of immature B-lymphocyte and T-lymphocyte precursors. Il-7 is produced mainly my fibroblasts and bone marrow stromal cells.

Some viruses cause infected host cells to secrete molecules that bind and tie up cytokines (def), preventing them from binding to normal cytokine receptors on host cells.

• Poxviruses cause infected host cells to secrete molecules that bind interleukin-1 (IL-1) and interferon-gamma (IFN-gamma).


• Cytomegaloviruses (CMV) cause infected host cells to secrete molecules that bind chemokines (def)."