Background The pineal hormone melatonin (MLT) exerts a variety of effects on the immune system. MLT activates Th1 lymphocytes and monocytes; moreover MLT enhances the production of inflammatory cytokines, like IL-1, IL-6, IL-12 and TNFa, as well as nitric oxide production.
Objectives Several symptoms of rheumatoid arthritis (RA), i.e. morning gelling, stiffness and swelling, are more evident in the early morning and might be related to the neuroimmunomodulatory effects exerted by MLT on synovitis. On the other hand, it is well known that MLT reaches its physiological serum peak level during the first hours of the morning.
Methods Nocturnal MLT serum levels (8 pm, 12 pm, 2 am, 4 am, 6 am, 8 am o’clock) were evaluated in ten RA patients (pts) (mean age 57 ± 13 SD ys) and in six healthy controls (cnts) (mean age 50 ± 18 SD ys). RA pts were taking only nonsteroidal antiinflammatory drugs and the mean disease duration was 4 ± 2 SD ys. MLT assay was performed by RIA and statistical analysis was carry out by nonparametric tests.
Results MLT serum levels at 8 pm and 8 am o’clock resulted higher in RA pts than in cnts (p < 0.05). The differences were more evident in the older RA pts (age > 60 ys) when compared to the younger ones (age < 60 ys). In both RA pts and cnts, MLT progressively increased from 8 o’clock pm to the first hours of the morning, reaching the peak level that gradually decreased (p < 0.02). However, MLT serum level reached the peak at least three hours before in RA pts than in cnts (p < 0.05); subsequently, in RA pts, MLT concentration showed a plateau lasting two-three hours. After 2 am o’clock MLT levels decreased similarly in both RA pts and cnts. MLT levels progressively decreased with ageing in all subjects; nevertheless, MLT serum levels resulted significantly lower only in RA pts at 4 am and 6 am o’clock (p < 0.05).
Conclusion The results of this study confirm the existence of a nocturnal rhythm of MLT also in RA pts, with the peak level in the early morning. However, RA pts showed higher mean MLT serum levels, that reached earlier the peak of concentration, and maintained the high levels for longer time when compared to cnts. The imbalance between cortisol serum levels (notably lower in RA pts) and MLT serum levels (higher in RA pts) might explain several clinical aspects related to the neuroimmunomodulatory effects on RA synovitis, such as morning gelling, stiffness and swelling.
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