Rheumatoid Arthritis and Sjögren’s Syndrome can be treated with human chorionic gonadotropin.

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The initial clue that hCG could be potentially useful in the treatment of RA and SS came from the clinical observations that these disease symptoms ameliorate during pregnancy. Further research revealed that hCG is responsible for this amelioration, Cells of immune system contain hCG receptors and their activation results in an alteration in the secretion of several cytokines. In addition, studies on two different animal models and a patient’s experience have reaffirmed the therapeutic value of hCG. The first animal model was streptococcal cell wall (SCW) induced arthritis in non-pregnant rats. When SCW was injected, rats will develop the signs and symptoms of RA within 2 days, which resemble human disease. They include, swelling, erythema and distortion of wrist and ankle joints, infiltration of pro-inflammatory cells into the joints, bone and cartilage destruction and the increased production of tumor necrosis factor (TNF) α, interleukin (IL)-6, IL-1ß, nitric oxide (NO) and inducible nitric oxide synthase (iNOS). Injection of either clinical grade or recombinant hCG, 2 days prior to SCW injection, resulted in a dose dependent decrease in the development of arthritis, blocked pathogenic changes typically associated with chronic disease phase, amelioration of symptoms, decreased infiltration of proinflammatory cells, cytokines, NO and iNOS levels, bone and cartilage destruction. The second animal model is non-obese diabetic (NOD) mice. These mice show a decreased salivary flow, invasion of CD4+T and B-lymphocytes into their salivary glands by 12-24 weeks of age. These changes are very much like those seen in salivary glands of SS patients. The hCG treatment from 6 to 12 weeks of age resulted in a marked increase in salivary secretion and a significant decrease in lymphocytes infiltration, damage to salivary gland parenchymal cells and a decrease in interferon γ, TNFα, IL-1ß, IL-10, iNOS and matrixmetalloproteinase-9 levels. The author is aware of a woman who had RA. Her symptoms ameliorated when she went through hCG weight loss program. They returned after the completion of the program. Suspecting that the benefits may be coming from hCG, she started taking low dose hCG. As a result, her symptoms ameliorated and can now drive long distances to visit her family and friends in U.S., which she could not do before. She is now enjoying the symptoms free life. The hCG, is a physiological hormone that has considerable advantages over the currently used immunosuppressive drugs. hCG, by comparison, is inexpensive. It can be made even cheaper by scaling up the production of recombinant hormone. It has minimal side effects and the common ones described from an intramuscular injection are the pain at the injection site, abdominal bloating, abdominal and pelvic pain, nausea, vomiting, etc. and they often do not require medical attention. If proven effective, there are many possibilities to improve hCG administration. These are long acting analogs and synthetic hCG mimetics for oral use and even regular hCG as lozenges. The active ingredient in them would slowly dissolve and rapidly gets into buccal blood circulation. Delivery of hCG by nanoparticle is another potential area for development. This type of delivery can reduce the dose and frequency of administration. Based on an overall data, we recommend conducting randomized placebo controlled clinical trials. Even though they will be expensive and time consuming, it is the least thing we can do to spare millions of people from the pain and suffering and the serious side effects of powerful immunosuppressive drugs. In addition, potentially, there is much to gain from these trials not only for RA and SS but also for other autoimmune diseases like, multiple sclerosis, thyroiditis and Crohn’s disease, which are also known to improve during pregnancy. hCG therapy may not work for all the autoimmune diseases, as there are more than 100 of them and they are not all the same. A good example is lupus erythematosus, which worsens during pregnancy. This disease is due to an increased antibody production by auto reactive B cells. It is possible that hCG may be effective not only on its own, but may also work in combination with lower doses of currently used immunosuppressive drugs. Such combinations could be more effective than single treatments, due to possible differences in their modes of action. In addition, combination therapies can be cost effective and reduce the overall toxicity and cost. As hCG is already being used in reproductive medicine, it is possible to optimize rather quickly the treatment conditions like, dose and frequency. In addition, the possibility of delivering the lower doses of hCG directly into joint synovial fluids of RA patients should be considered. This route can reduce the dose and mitigate the side effects. The potential hCG use for the treatment of RA and SS suggests that its administration during assisted reproductive technologies could slow down the progression of autoimmune diseases, a secondary benefit that patients and physicians may not realize. Finally, as any other treatment, hCG therapy may not work for every patient. Thus, it should not be considered as a panacea. Instead, it should be considered to have the potential to become an important part of physicians’ tool box to treat patients suffering with RA, SS and few other autoimmune diseases.

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