Effect of melatonin treatment on 24-h variations in responses to mitogens and lymphocyte subset populations in rat submaxillary lymph nodes

Wistar male rats were injected s.c. with melatonin (30 mu g) or vehicle, 1 h before lights off, for 11 days. Ten days after beginning melatonin treatm ent, rats received Freund's complete adjuvant or its vehicle s.c., and afte r 2 days, they were sacrificed at six different time intervals throughout a 24-h cycle. The mitogenic effect of lipopolysaccharide (LPS) and concanava lin A (Con A), the activity of ornithine decarboxylase (ODC) and the relati ve size of lymphocyte subset populations were measured in submaxillary lymp h nodes. In control rats, the mitogenic effects of LPS and Con A and ODC ac tivity peaked during the afternoon. Injection of Freund's adjuvant induced a 10-h shift in the diurnal rhythm of the mitogenic effect of LPS to attain maximal values at night. Melatonin pretreatment blunted the daily variatio ns in the mitogenic activity of Con A or LPS and, when given to Freund's ad juvant-injected rats, augmented mesor and amplitude of diurnal rhythm in OD C activity. Maxima in B cell number occurred at night whereas those of T an d B-T cell number occurred during the afternoon. During the early phase of immunization tested, the number of B cells augmented and the amplitude of i ts diurnal rhythmicity increased both after immunization and following mela tonin pretreatment. Maxima of 24-h rhythms in CD4+ and CD4+/CD8+ cell popul ations occurred during the afternoon while those of CD8+ cells occurred at late night. Melatonin significantly augmented CD4+ cell number and decrease d CD8+ cell number; it therefore augmented the CD4+:CD8+ ratio. The results suggest that pretreatment with a pharmacological dose of melatonin exerts immunomodulating effects at an early, preclinical, phase of Freund's adjuva nt-induced arthritis in rats.