Effects and mechanisms of melatonin on inflammatory and immune responses of adjuvant arthritis rat
1Institute of Clinical Pharmacology, Anhui Medical University, Hefei 230032, China. chenq2001@163.net
Aim:
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.
