Rheumatoid arthritis and the biological clock

Abstract

Rheumatoid arthritis (RA) is an autoimmune disease of unknown cause and a chronic and progressive inflammatory disorder ensuing in genetically predisposed subjects, characterized by synovitis causing joint destruction, as well as inflammation in body organ systems, leading to anatomical alteration and functional disability. Immune competent cells, deregulated synoviocytes and cytokines play a key role in the pathophysiological mechanisms. The immune system function shows time-related variations related to the influence of the neuroendocrine system and driven by the circadian clock circuitry. Immune processes and symptom intensity in RA are characterized by oscillations during the day following a pattern of circadian rhythmicity. A cross-talk between inflammatory and circadian pathways is involved in RA pathogenesis and underlies the mutual actions of disruption of the circadian clock circuitry on immune system function as well as of inflammation on the function of the biological clock. Modulation of molecular processes and humoral factors mediating in RA the interplay between the biological clock and the immune response and underlying the rhythmic fluctuations of pathogenic processes and symptomatology could represent a promising therapeutic strategy in the future.

Keywords::

• circadian
• clock gene
• immune system
• rheumatoid arthritis
• rhythm

Acknowledgements

We apologize for any relevant studies and pertinent references that we have not commented on due to space limitations.

Financial & competing interests disclosure

This work was supported by the ‘5x1000’ voluntary contribution and by grants to GM from the Italian Ministry of Health (RC1203ME46 and RC1302ME31) through Department of Medical Sciences, Division of Internal Medicine and Chronobiology Unit, IRCCS Scientific Institute and Regional General Hospital ‘Casa Sollievo della Sofferenza’, Opera di Padre Pio da Pietrelcina, San Giovanni Rotondo (FG), Italy. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Key issues

• Rheumatoid arthritis is characterized by synovitis of small joints of hands and feet, as well as chronic inflammation of the skin, eyes, lungs, heart and blood vessels.

• Cytokines, T and B lymphocytes and autoantibodies are crucial players in the inflammatory process.

• The intensity of symptomatology oscillates during the day and pain and stiffness are greater in the morning after waking up, in line with the levels of inflammation mediators.

• The immune system function is characterized by rhythmic oscillations with a period of 24 h defined circadian.

• The circadian rhythmicity of immune responses and inflammatory processes is driven by the biological clock.

Notes