The pathogenesis of rheumatoid arthritis: pivotal cytokines involved in bone degradation and inflammation.
Proinflammatory cytokines, notably interleukin 1 (IL-1) and tumor necrosis factor-alpha (TNF-alpha), play an important role in initiating and perpetuating inflammatory and destructive processes in the rheumatoid joint. These cytokines regulate many nuclear factor kappaB inducible genes that control expression of other cytokines, cell adhesion molecules, immunoregulatory molecules, and proinflammatory mediators. The expression of cyclooxygenase-2 and inducible nitric oxide synthase (iNOS) and thereby production of prostaglandins (PG) and NO are regulated by cytokines. PGE2 and NO further promote inflammation and likely participate in destructive mechanisms in the rheumatoid joint. In some experimental systems, the effects of IL-1 and TNF-alpha appear synergistic, and correspondingly, concomitant inhibition of both cytokines provides greater than additive antiarthritic effects. Although the actions of IL-1 and TNF-alpha show a large degree of overlap, some differences have been observed in animal models. However, in patients with active rheumatoid arthritis, blockade of either cytokine results in clinical improvement and less radiographic progression.
Bingham
Clifton O
CO
New York University School of Medicine, Department of Rheumatology and Medicine, NYU Hospital for Joint Diseases, NY 10003, USA. clifton.bingham@med.nyu.edu
D001172:Arthritis, Rheumatoid / Q000378:metabolism* / Q000473:pathology*; D002908:Chronic Disease; D051546:Cyclooxygenase 2; D016207:Cytokines / Q000378:metabolism*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007249:Inflammation / Q000503:physiopathology*; D018836:Inflammation Mediators / Q000032:analysis*; D007375:Interleukin-1 / Q000378:metabolism; D007527:Isoenzymes / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins; D019001:Nitric Oxide Synthase / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D012680:Sensitivity and Specificity; D012720:Severity of Illness Index; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D016207:Cytokines; D018836:Inflammation Mediators; D007375:Interleukin-1; D007527:Isoenzymes; D008565:Membrane Proteins; D014409:Tumor Necrosis Factor-alpha; C496319:NOS2 protein, human; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases