Rheumatoid arthritis, cytokines and hypoxia. What is the link?
Rheumatoid arthritis (RA) is a chronic systemic inflammatory disorder that affects approximately 1% of the population, in a female to male ratio of 3:1. The disease can occur at any age, but it is most common among those aged 40-70 years. Despite many years of study, the etiology of RA is still undefined. However, with increased understanding of the immune system the pathogenesis of RA has become clearer. A large bulk of data suggests that T lymphocytes and macrophages play a critical role in the initiation and perpetuation of synovial inflammation. Recently, the cytokine profile of T helper cells has been associated with the disease, the cytokine repertoire of inflamed synovia is categorized as that of T helper 1 response. Moreover, in RA elevated levels of pro-inflammatory or inflammatory cytokines such as Tumor Necrosis Factor - alpha (TNF-alpha) and Interleukin -1 beta (IL-1beta) have been detected. Hypoxia up-regulates TNF-alpha and IL-1beta; therefore, considerable research interest has been focused on the biological consequences of the hypoxic nature of the rheumatoid synovium. Hypoxia might underlie the functional polarization of the T cells and cytokine production, and thus may contribute to the progression and persistence of the disease. In this short review, we discuss our current knowledge of the link between cytokines and RA and the role of hypoxia in the pathogenesis of the disease.
Al-Shukaili
Ahmed K
AK
Department of Microbiology and Immunology, College of Medicine and Health Sciences, Sultan Qaboos University, Al Khod, Muscat, Sultanate of Oman.
Al-Jabri
Ali A
AA
D000328:Adult; D000367:Age Factors; D000368:Aged; D001172:Arthritis, Rheumatoid / Q000453:epidemiology / Q000209:etiology* / Q000276:immunology / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D015687:Cell Hypoxia; D016207:Cytokines / Q000502:physiology*; D018450:Disease Progression; D005260:Female; D006801:Humans; D007596:Joints / Q000473:pathology; D008264:Macrophages; D008297:Male; D008875:Middle Aged; D018384:Oxidative Stress; D012737:Sex Factors; D013583:Synovial Membrane / Q000276:immunology / Q000473:pathology; D013601:T-Lymphocytes
D016207:Cytokines