The pineal and regulation of fibrosis: pinealectomy as a model of primary biliary cirrhosis: roles of melatonin and prostaglandins in fibrosis and regulation of T lymphocytes.

Pinealectomy leads to increased formation of fibrous tissue in the abdominal cavity, increased skin pigmentation and elevated cholesterol and alkaline phosphatase levels. It also leads to reduced formation and/or action of prostaglandin (PG) E1 and thromboxane (TX) A2. PGE1 plays an important role in enhancing function of T suppressor lymphocytes which control overactive antibody-producing B lymphocytes. In primary biliary cirrhosis there are increased skin pigmentation, hepatic fibrosis, elevated cholesterol and alkaline phosphatase levels, defective T lymphocytes and hyperactive B lymphocytes. Primary biliary cirrhosis may be a pineal deficiency disease. Serotonin is important in the pineal and the serotonin antagonist methysergide may cause retroperitoneal fibrosis by interfering with pineal function. There is a good deal of other evidence which suggests that melatonin PGE1 and TXA2 are important in the regulation of fibrosis in other situations such as "collagen" diseases, lithium-induced fibrosis and cardiomyopathies. This suggests that enhancement of formation of PGE1 and TXA2 may be of value in diseases associated with excess fibrosis and defective T suppressor cell function. PGE1 levels may be raised by zinc, penicillin, penicillamine and essential fatty acids. TXA2 levels may be raised by low dose colchicine. These new approaches to treatment may prove safer and more effective than existing ones. They may be of value in disorders such as cardiomyopathy, Hodgkin's disease and other lymphomas, multiple sclerosis, Crohn's disease, atopy and other diseases in which defective T cell function is suspected.