Cytokine Inflammation and Management in Fibromyalgia and Chronic Fatigue Syndrome
By John W. Addington •
July 24, 2002
Inflammation in an otherwise healthy person is a natural response to injury or infection and is part of the normal healing process. Chronic inflammation, on the other hand, can reflect an improperly functioning immune system. Many researchers feel that chronic inflammation along with an altered immune system may either be the cause or contribute to fibromyalgia (FM) and chronic fatigue syndrome (CFS) symptoms. Fortunately, some treatment options are emerging to manage such inflammation and thus limit the discomfort and pain brought on by these ailments.
Chemical messengers called cytokines form an integral part element of the immune system. As messengers, cytokines tell other immune cells to activate, grow or even die. Dr. Lionel Ivashkiv, a rheumatologist, explains that “cytokines regulate the immune system responses and can drive the inflammatory process.” In this and other ways, cytokines aid white blood cells in fighting infection.
Not all cytokine involvement is positive, however. It is thought that highly elevated cytokine levels found in the brains of Alzheimer's patients contribute to their symptoms. Abnormal cytokine activity in rheumatoid arthritis leads to damaged joints. Cytokine disturbances have been implicated, but not always well understood, in other autoimmune disorders as well.
According to Dr. Ivashkiv, there are hundreds of cytokines and their network of activity is very complicated. He states, "It has become clear that the cytokine networks can be perturbed at different levels and have very significant and strong effects on the overall autoimmune process."
Elevated Cytokines in FM and CFS
Besides inflammation, excess cytokines can bring on flu-like symptoms including fever, achiness, and fatigue. In studies, doctors found that fibromyalgia symptoms temporarily resulted when particular cytokines were administered to persons who did not normally have the syndrome. Additionally, some cytokines are known to increase substance P, which transmits pain messages. Thus, it is no wonder that researchers wanted to know whether cytokine levels were elevated in persons with fibromyalgia.
While the latest research published found some fibromyalgia patients had excessive cytokines, the results are considered preliminary only because of the small number of patients studied. Dr. Daniel Wallace headed up an investigation in Los Angeles discovering that patients sick for over two years were more likely to have high cytokines levels. Although the researchers found altered cytokine production in early-stage fibromyalgia, the cytokines were seen to increase with the duration of the sickness. The authors of this work, published in the July 2001 issue of the journal Rheumatology, conclude that their results underscore "the argument for earlier, aggressive intervention to prevent a chronic pattern from developing."
It has not yet been determined, however, whether elevated cytokines are the direct cause of fibromyalgia or merely secondary to another factor. Factors that could contribute to cytokines increase and be a more direct cause of the ailment are other immune problems, abnormal hormone activity, or sleep disturbances. For example, elevated cytokines levels can be induced through sleep deprivation, so perhaps disordered sleep could be the real root of fibromyalgia.
Immune dysfunction as a contributing cause to the related condition of CFS has also been researched. Dr. Nancy Klimas is an immunologist in Miami who has spent considerable time studying CFS. She explains, "with regard to the immune system, we have a system that is hyperactive but not working properly." As part of this hyperactive state, Dr. Klimas has seen unusually high amounts of cytokines in CFS patients, and she feels that this in turn may cause the hormonal imbalances of such persons.
Other researchers feel the same about this possible cause of CFS, despite the mixed result seen in studies performed. Dr. Stephen Straus writes, "An immune disturbance of some type, though, is in line with one favored theory that many of the symptoms of chronic fatigue syndrome derive from excessive cytokine release."
Management of Cytokine Inflammation
While cytokine related drug therapies are starting to have some benefit for conditions like rheumatoid arthritis, that is not the case yet for FM and CFS. Dr. Roberto Patarca has extensively studied the topic and he says medications are not available "mainly because nobody knows which cytokine system in particular to target and because of the [complexity] of the cytokine network components." But research on this topic continues. And, a number of cytokine altering medications are currently being developed. So, it may be that in the not too distant future, medications to regulate cytokine difficulties for FM and CFS may exist.
Drs. Charles Lapp and Paul Cheney both recommend hydrotherapy as a means of reducing cytokine levels. They recommend 15-30 minutes of being vertically immersed (standing) in water that is around 85 degrees [Fahrenheit], 2-3 times a week. Dr. Lapp explains, "when the temperature of the water is 85-95 degrees, it is cooler than your body temperature, so you are cooling down the core. When you cool down the core, it cuts down on the cytokines as well, and those cause the flu-like symptoms."
The rationale behind this therapy is that the increased pressure at your feet, which decreases upward, causes a squeezing action in your lymph system. This forces lymph fluids to enter your blood stream and signals your body that enough cytokines are already circulating in your blood stream. This, in turn, results in downregulation of your immune system. Regarding this process, the book, Chronic Fatigue Syndrome: A Treatment Guide, relates, "In patients experiencing the effects of excess cytokine production, downregulation of immune system chemicals can provide tremendous relief."
The Life Extension magazine notes that the DHA fish oil is the best documented supplement to suppress certain inflammatory cytokines. Actually, supplements containing any essential fatty acids are very important. These would include evening primrose oil, borage oil, flax seed oil, and Omega 3 and 6 [essential fatty acids]. Other anti-inflammatory supplements include Vitamins B, C, E, and K, and DHEA. Herbs that act as natural inflammation fighters are nettle leaf, boswellia, cat's claw and tumeric.
Dr. Zoltan Rona recommends bovine colostrum as a "powerful immune system modulator—stimulating a sluggish immune system or dampening an overactive immune response." He also encourages the use of digestive enzymes whether pancreatic or plant derived, particularly bromelain, because of how well these supplements counter inflammation.
To stabilize an overactive immune system, Dr. Paul Cheney advocates the use of undenatured whey protein (as in Pro Health's ImmunPlex). Whey protein is useful because of its ability to replenish proper glutathione levels that are low in some with CFS. Dr. Cheney believes that deficient glutathione coupled with excessive cytokines is what promotes activation of harmful microbes like EBV [Epstein-Barr Virus], HHV-6 [Human Herpes Virus-6] as well as chlamydia pneumonia, candida and other mycoplasmas.
In a small study on CFS patients, Cheney found whey protein to be very effective in wiping out these harmful microorganisms. Thus, by raising glutathione levels, undenatured whey protein apparently counteracts some of the damaging effects of excessive cytokines.
Diet can play a significant roll in managing cytokine related symptoms. This is true both in what foods are best to consume and those that should be avoided. As to which foods to avoid, many researchers are finding that patients with FM and CFS may have food sensitivities that can aggravate their symptoms. Food sensitivities, also called food intolerance, are not the same as food allergies but can nonetheless contribute to illness.
Research published recently in the Lancet medical journal involved a small group of patients with CFS in Norway, who for over four years had benefited from substantial improvement by dietary exclusion of wheat and milk. After reintroducing these foods into their diets, doctors found a "striking rise" in the patients' cytokine levels along with an increase in abdominal discomfort and joint and muscular pain. These doctors state that "the pronounced increase in release of [particular cytokines], suggests that food intolerance is accompanied by a general immune activation…possibly related to the more general symptoms in these patients."
The foods most likely to be the culprits when it comes to intolerance are wheat, yeast, milk, sugar, peanuts, corn, eggs, citrus, alcohol, caffeine and soy. Various tests can detect food sensitivities but the elimination and challenge method is one of the best means to determine this kind of problem. This involves completely avoiding the suspect food (including traces of it in other foods) for 7-10 days, and then noting if symptoms reoccur when the food is reintroduced into the diet.
Prime foods that can counter cytokine inflammation are coldwater fish such as salmon, trout, mackerel, sardines, swordfish, shark, cod and halibut. These fish are beneficial because of the omega-3 fatty acids they contain. It is good to include flax seed, evening primrose oil, and borage oil in one's diet also because of their anti-inflammatory properties. Additionally, fresh pineapple, fresh papaya, spinach, blueberries, strawberries and onions are useful.
Strong preliminary evidence leads many researchers to believe that excess cytokines may be responsible for CFS and FM symptoms. A degree of relief may be possible through present therapies, supplements and diet regimes. As more research reveals in greater detail the exact nature of immune dysfunction in these ailments, medications will likely be developed to more effectively alleviate cytokine inflammation in CFS and FM.
AFSA, Cytokine Abnormalities Official, AFSA Update, 8(2) (2002)
Balch & Balch, Inflammation in Prescription for Nutritional Healing (2000)
Cheney, Dr. Paul Cheney Discusses Benefits of Undenatured Whey Protein (2000)
Faloon, Chronic Inflammation, Life Extension Magazine (Jan. 2002)
Klimas, Cytokine and Other Immunologic Markers in Chronic Fatigue Syndrome and Their Relation to Neuropsychological Factors, Applied Neuropsychology, 8(1);51 (2001)
Lapp, The Treatment of CFS-Perspective of a Private Specialty Practice in Charlotte, N.C. (2000) http://www.immunesupport.com/library/showarticle.cfm?ID=2926
Logan & Wong, Chronic Fatigue Syndrome: Oxidative Stress and Dietary Modifications, Alternative Medicine Review, 6(5):450 (2001)
Mullington, et al., Mediators of Inflammation and Their Interaction with Sleep: Relevance for Chronic Fatigue Syndrome and Related Conditions, Annals of the New York Academy of Sciences, 933:201 (2001)
Patarca, Concise Encyclopedia of Chronic Fatigue Syndrome (2000)
Patarca, Cytokines and Chronic Fatigue Syndrome, Annals of the New York Academy of Sciences, 933:185 (2001)
Rheumatology.HSS.edu, Cytokines in Inflammatory Disease (Interview of Lionel Ivashkiv) (2002) http://www.rheumatology.hss.edu/phys/interviews/ivashkiv_int_tran.asp
Straus, Chronic Fatigue Syndrome, in Harrison’s Principles of Internal Medicine. 14th ed. (1998)
Teitelbaum, Food Allergies, in From Fatigued to Fantastic (2001)
Thompson, Chronic Fatigue Syndrome and Food Allergies: How Diet Could Be Effecting Your Symptoms, (2002) http://www.immunesupport.com/library/showarticle.cfm?ID=3334
Verrillo & Gellman, Hydrotherapy, in Chronic Fatigue Syndrome: A Treatment Guide (1998)
Wallace, et al., Cytokines Play an Aetiopathogenetic Role in Fibromyalgia: a Hypothesis and Pilot Study, Rheumatology, 40:743 (2001)
West & Maes, Neuroendocrine and Immune Aspects of Fibromyalgia, BioDrugs, 15(8):521 (2001)
Zimmerman, Fight Inflammation, Taste for Life (July 2002)
Zoltan, A Natural Fibromyalgia Treatment Protocol, (2002) http://www.immunesupport.com/library/showarticle.cfm?ID=3364
(c) 2002 Pro Health Inc., and ImmuneSupport.com.
| (1 existing comment)
|Posted by: DeadPoet
Dec 12, 2011
Great information. The one angle the author fails to mention is the role microbes play on our immune systems (specifically Th1 vs Th2 response, cytokine production, NK cells, macrophages, etc etc)
Lyme Disease (and it's fellow co-infections) will disrupt the immune system to a point of dysfunction and enter "auto-immune" issues.
Treating the underlying cause is always the most important aspect to gaining our health back. And for CFS/Fibromyalgia patients look no further than microbes (Lyme/borrelia, bartonella, babesia, mycoplasma, parasites, metal toxicity)
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