A case of melatonin-induced biochemical flare in a patient with primary sclerosing cholangitis with features of autoimmune hepatitis

Melatonin (N-acetyl-5-methoxy-triptamine) is the major product of the pineal gland; however, it has also been identified in a large number of extrapineal organs including the gastrointestinal tract, cornea, bone marrow, lymphocytes, etc. [1]. Melatonin has well-known anti-oxidative, oncostatic, and anti-aging properties and numerous experimental and clinical data have established its beneficial effects [2–4]. Melatonin exerts some of its physiological effects in immune cells through two G-protein-coupled specific membrane receptors: MT1 (cAMP signalling pathway) and MT2 (cGMP signalling pathway). There is now evidence that melatonin possesses important immunoenhancing properties, mostly underlined in immunodepressed situations [3], and it may counteract the immunosuppressive effect of corticotherapy. Melatonin promotes a Th1-mediated response (Th1 cells produce far more interferon  (IFN-) and interleukin 2 (IL-2) than Th2 cells), thereby activating inflammatory pathways. However, melatonin can also stimulate Th2 cells which produce far more IL-4 and IL-10 than do the Th1 cells. Th2 cells stimulate antibody production via B lymphocytes and down regulate Th1 cells, and thus they may inhibit some Th1-mediated inflammatory responses [5–7].
Although melatonin is one of the least toxic substances known, its pharmacological effect on some autoimmune diseases such as rheumatoid arthritis and Crohn’s disease at this point is controversial [8]. In 1997, Hong et al. [9] reported a patient who developed autoimmune hepatitis after beginning melatonin therapy for the treatment of insomnia. Recently, Fourman et al. [10] reported a case of autoimmune hepatitis that developed in a 50-year-old man after starting ramelteon, a melatonin agonist, for insomnia. Here we present a patient with primary sclerosing cholangitis (PSC) with features of autoimmune hepatitis (AIH) and associated with ulcerative colitis, who developed a severe elevation of liver enzymes following the use of melatonin in two separate courses.
The patient was a 25-year-old female with a history of autoimmune hepatitis diagnosed at the age 23 years in a local hospital and treated with corticosteroids and azathioprine for 2 years. She denied taking any other medications as well as supplements for depression including St John’s wort, which has been known to cause serious interactions with some drugs. Because she experienced no response to the therapy she was referred to our hospital. On...


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