Circadian rhythms in arthritis: hormonal effects on the immune/inflammatory reaction.

Biological signaling and rhythms occur in a complex network with participation and interaction of the central nervous system, the autonomic nervous system, the endocrine glands, peripheral endocrine tissues and the immune system. It is a clinical observation that patients affected by chronic immune/inflammatory conditions (i.e. rheumatoid arthritis/RA) exhibit circadian, circamensual (females) and circannual rhythms of disease-related symptoms. Proinflammatory cytokines exhibit a peculiar rhythmicity, in particular serum TNF and serum IL-6, and together with other relevant immunological parameters display an elevation in the early morning hours in patients with RA. As a matter of fact, RA patients particularly experience joint pain, morning stiffness, and functional disability in the early morning hours. Since circadian rhythmicity of neuroendocrine pathways is closely coupled to immune/inflammatory reactions, new aspects at least concerning RA management are suggested. In particular, further investigations will indicate whether timed release of immunosuppressive/antiinflammatory drugs will have increased efficacy and whether dosages can be reduced below critical levels above which adverse events appear.