Cytokines and inflammation and how they influence depression and various medical diseases
Reduction or influence of herbs and diet, food
July 10 2016 by
Ray Sahelian, M.D.

Definition: A cytokine is a small protein released by cells that has a specific effect on the interactions between cells and on communications between cells. Cytokines include a number of groups which are called interleukins, lymphokines and cell signal molecules, such as tumor necrosis factor and the interferons, which trigger inflammation and respond to infections. There are both pro-inflammatory cytokines and anti-inflammatory cytokines. They are involved in almost every disease, and the manipulation of cytokine levels through diet or natural herbal supplements is an exciting field to explore. For instance, the flavonoid luteolin could reduce cytokine levels.

Cytokines and depression, mood changes
Clinical and experimental studies indicate that stress and depression are associated with the up-regulation of the immune system, including increased production of pro-inflammatory cytokines. When administered to patients or laboratory animals, some of these cytokines induce typical symptoms of depression. It is known that cytokines influence brain neurotransmitters and the activity of the hypothalamic-pituitary-adrenal axis, both of which are disturbed in depression. Therefore some cases of low mood and low energy / motivation are due to elevated levels of these proteins.

Influence of dietary supplements, herbs, vitamins
Supplementation with omega-e fatty acids, mostly found in fish and fish oils, can help reduce cytokine production.

Q. Can you tell me if saw palmetto or the herbal extract curcumin reduce cytokine levels?
   A. It appears in some studies that curcumin can reduce serum TNF-alpha and interleukin levels. We have not seen studies regarding the interaction of saw palmetto with cytokines.

I just had a cytokine test done on my levels of cytokines, and 6 out of 8 were undetectable: IL 2,4,5,10,12,Tnf a. But IL 6 and Gamma interferon were in the normal ranges. I have long term severe CFS chronic fatigue syndrome. Things I used to be able to take now make me much more tired, bedridden, with a flu like malaise. Even things like beta carotene, vitamin A, NAC, ALA, antiviral and antibacterial herbs, immune boosters, B12, probiotics. The list goes on. I can take Co q10, vitamin E, PPC, PPS, Fish oil, enzymes, and other things. The normal CBC with Differential/Platelet tests like neutrophils, basophilss, WBCs etc., were all normal. So, its the cytokines I lack. Any idea would be greatly appreciated, for I am mostly bedridden now.
   A. There is not research enough yet to know exactly how to manipulate different ones and for practical purposes that is not as important as taking a comprehensive dietary and lifestyle changes that have an overall global influence on inflammatory markers in the body.

Echinacea and Cytokines
Cytokine production in leukocyte cultures during therapy with Echinacea extract.
J Clin Lab Anal. 1996.
We measured the levels of the cytokines IL-1-alpha, IL-1-beta, IL-2, IL-6, TNF-alpha, and IFN-gamma in culture supernatants of stimulated whole blood cells derived from 23 tumor patients undergoing a 4-week oral treatment with a spagyric extract from Echinacea angustifolia, Eupatorium perfoliatum, and Thuja occidentalis (Echinacea complex). All patients had had curative surgery for a localized solid malignant tumor. Blood was taken before treatment and after 2 and 4 weeks of therapy. Twelve untreated tumor patients at the same clinical stage, also after curative surgery, served as a control group. In the blood cell cultures of all patients, a rather wide range of cytokine levels was found. After therapy with Echinacea complex, no significant alteration in the production of the cytokines could be seen in comparison to the controls, and also the leukocyte populations remained constant. We conclude that at this application and dosage, the therapy with Echinacea complex has no detectable effect on tumor patients' lymphocytes activity as measured by their cytokine production.

Garlic influence
Urol J. 2014. The effect of garlic powder on human urinary cytokine excretion. To evaluate the effects of orally administered dehydrated garlic powder on cytokine excretion in the urinary tract. A total of 60 healthy volunteers, randomized into 3 groups, were given a single oral dose of 1 g or 3 g of dehydrated garlic powder or placebo. Oral intake of doses of garlic traditionally used for daily supplementation increases urinary levels of IL-12, which is a potent stimulator of T helper cell 1 (Th-1) immune responses. This observation encourages further studies investigating the immunostimulatory role of garlic in the urinary tract.

Cytokine and Allergy
Allergic diseases have been closely related to Th2 immune responses, which are characterized by high levels of interleukin IL-4, IL-5, IL-9 and IL-13. These cytokines orchestrate the recruitment and activation of different effector cells, such as eosinophils and mast cells. These cells along with Th2 cytokines are key players on the development of chronic allergic inflammatory disorders, usually characterized by airway hyperresponsiveness, reversible airway obstruction, and airway inflammation. Accumulating evidences have shown that altering cytokine-producing profile of Th2 cells by inducing Th1 responses may be protective against Th2-related diseases such as asthma and allergy.

Cancer Treatment
Cytokine -based immunotherapy has been investigated for cancer treatment. However, so far most cytokine -based therapy trials have fallen short of expectations. One of main obstacles is the difficulty to achieve therapeutically relevant dosage in patients without generating excessive normal tissue toxicity.

When infection occurs, white blood cells send cytokines to marshal defenses in the body. Cytokines tell blood vessels in the brain to make a second hormone, prostaglandin E2. Prostaglandin E2 acts on the hypothalamus, an area of the brain that controls basic functions like eating, drinking, sex and body temperature. Aspirin acts on all prostaglandin receptors in the body.

Cytokines and heart disease
There is an association between increased heart disease with proinflammatory cytokines. Many germs including bacteria, protozoa and viruses have been associated with heart disease in patients, and are able to induce similar disease in animal models. Recognition of germs by the innate immune system leads to release of proinflammatory cytokines that both reduce infection and increase chronic inflammatory heart disease.

Congestive heart failure
Elevated circulating concentrations of proinflammatory cytokines may contribute to the pathogenesis of congestive heart failure (CHF). In vitro studies suggest that vitamin D suppresses proinflammatory cytokines and increases antiinflammatory cytokines. There may be an impaired vitamin D–parathyroid hormone axis in the progression of CHF.

Repetitive Motion chronic pain
Early nerve damage caused by repetitive motion on the job can cause "sick worker" syndrome, a fatigue or depression that can be mistaken for poor work performance. The study done on rats found that nerve injuries caused by low-force, highly repetitive movement -- a condition called repetitive strain injury, which is common to typists, pianists and meatpackers, among other professions -- can be blamed on increased production of proteins known as cytokines. Cytokines show up in injured nerves as early as three weeks after the first signs of cell stress. Cytokines also are known to spark symptoms of malaise and the study concludes that an onslaught of these proteins affected the rats' psychosocial responses. With so many cytokines entering the blood stream so early, some apparently traveled to the brain, sparking the rat version of "sick worker" syndrome.

Cytokines and Chronic Pain
Low blood levels of two anti-inflammatory proteins could be key to chronic pain. Low concentrations of two cytokines, IL-4 and IL-10, were found in patients with chronic widespread pain, according to a German study published in the 2006 issue of Arthritis & Rheumatism. Cytokines are proteins that act as messengers between cells. The study included 40 patients who'd received intravenous immunoglobulin (IVIG) as a novel treatment for pain that hadn't responded to standard therapy and another 15 patients who did not receive IVIG. The study also included a control group of 40 healthy people. Blood samples were collected from all the study volunteers, and the pain patients were asked to rate their pain, fatigue, mood and cognitive function. Compared with the control group, the 40 pain patients had significantly lower levels of the cytokines IL-4 and IL-10. The 15 patients in the second group had similar results, although the difference in their levels of IL-10 compared to people in the control group was not statistically significant. Several factors may be involved in low levels of these cytokines and how they influence pain, the study authors said. They noted that previous studies have shown that IL-10 reduces sensitivity to pain and that IL-4 can also dull pain response.

Cytokine modifying biologic drugs
Humira (adalimumab), Remicade (infliximab), and Enbrel (etanercept) are rheumatoid arthritis drugs and have comparable effectiveness and safety. These biologic drugs either block or supplement immune system chemicals called cytokines. The three drugs all work by blocking a cytokine called tumor necrosis factor. Biologics, however, also have the potential for rare but severe side effects such as serious infections or cancers. Another biologic drug, Kineret (anakinra), which blocks a cytokine called interleukin-1, appears to be less effective than the other three drugs. Journal of Rheumatology, 2006.