PATHOGENIC RESPONSES OF BRADYKININ SYSTEM IN CHRONIC INFLAMMATORY RHEUMATOID DISEASE

Excessive release of kinin (BK) in the synovial fluid can produce oede ma, pain and loss of functions due to activation of B-1 and B-2 kinin receptors. Activation of the kinin forming system could be mediated vi a injury, trauma, coagulation pathways (Hageman factor and thrombin) a nd immune complexes. The activated B-1 and B-2 receptors might cause r elease of other powerful non-cytokine and cytokine mediators of inflam mation, e.g., PGE(2), PGI(2), LTs, histamine, PAF, IL-1 and TNF, deriv ed mainly from polymer phonuclear leukocytes, macrophages, endothelial cells and synovial tissue. These mediators are capable of inducing bo ne and cartilage damage, hypertrophic synovitis, vessel proliferation, inflammatory cell migration and, possibly, angiogenesis in pannus for mation. These pathological changes, however, are not yet defined in th e human model of chronic inflammation. The role of kinins and their in teracting inflammatory mediators would soon start to clarify the detai led questions they revealed in clinical and experimental models of chr onic inflammatory diseases. Several B, and B, receptor antagonists are being synthesized in an attempt to study the molecular functions of k inins in inflammatory processes, such as rheumatoid arthritis, periodo ntitis, inflammatory diseases of the gut and osteomyelitis. Future dev elopment of specific potent and stable B, and B, receptor antagonists or combined B, and B, antagonists with y-IFN might serve as a pharmaco logical basis for more effective treatment of joint inflammatory and r elated diseases.