Effects and mechanisms of melatonin on inflammatory and immune responses of adjuvant arthritis rat.
OBJECTIVE
To study the effects of melatonin on inflammatory and immune responses and its mechanisms.


METHODS
The model of adjuvant-induced arthritis (AA) rat was induced by Freund's complete adjuvant (FCA); the thymocyte proliferation and IL-2 production were assayed by 3-(4,5-2dimethylthiazal-2yl)2,5-diphenyltetrazoliumbromide (MTT) and activated mouse splenocytes proliferation, respectively; cAMP and methionine-enkephalin (Met-Enk) level were determined by competitive protein binding assay (CPBA) and radioimmuno-assay, respectively.


RESULTS
There was a marked inflammatory response in AA model, which was accompanied by the decreases of thymocyte proliferation and IL-2 production simultaneously. The prophylactic and therapeutic administration of melatonin (1, 10 and 100 microg kg(-1), ig x 7 days) inhibited the inflammatory response and enhanced thymocytes proliferation and IL-2 production significantly in AA rats. In vitro, melatonin, at the concentrations of 10(-7) and 10(-6) mol l(-1) could enhance the thymocyte proliferation in AA rats. The cAMP level stimulated by forskolin (F, a selective adenylate cyclase [AC] activator) in AA rats was higher than that in the control groups. Melatonin (10(-10) or 10(-6) mol l(-1)) had down-regulation on the above increased cAMP levels, which could be abolished by pertussis toxin (PT). Meanwhile, the decrease of thymocyte proliferation in AA rats had a marked relation with the decrease of Met-Enk level in these thymocytes, melatonin (10(-10) or 10(-6) mol l(-1)) could markedly enhance the Met-Enk level, which were blocked by nifedipine, a Ca2+ channel antagonist.


CONCLUSIONS
Melatonin possesses anti-inflammatory and immunoregulatory actions, the G protein-AC-cAMP transmembrane signal and Met-Enk release in thymocyte are important mechanisms of this action.
Chen
Qun
Q
Institute of Clinical Pharmacology, Anhui Medical University, Hefei 230032, China. chenq2001@163.net
Wei
Wei
W
D000818:Animals; D001169:Arthritis, Experimental / Q000188:drug therapy* / Q000276:immunology; D000242:Cyclic AMP / Q000096:biosynthesis; D004744:Enkephalin, Methionine / Q000096:biosynthesis; D008213:Lymphocyte Activation / Q000187:drug effects; D008550:Melatonin / Q000494:pharmacology* / Q000627:therapeutic use; D051379:Mice; D008810:Mice, Inbred C57BL; D051381:Rats; D017207:Rats, Sprague-Dawley
D004744:Enkephalin, Methionine; D000242:Cyclic AMP; D008550:Melatonin