Pathogenic responses of bradykinin system in chronic inflammatory rheumatoid disease.
Excessive release of kinin (BK) in the synovial fluid can produce oedema, pain and loss of functions due to activation of B1 and B2 kinin receptors. Activation of the kinin forming system could be mediated via injury, trauma, coagulation pathways (Hageman factor and thrombin) and immune complexes. The activated B1 and B2 receptors might cause release of other powerful non-cytokine and cytokine mediators of inflammation, e.g., PGE2, PGI2, LTs, histamine, PAF, IL-1 and TNF, derived mainly from polymorphonuclear leukocytes, macrophages, endothelial cells and synovial tissue. These mediators are capable of inducing bone and cartilage damage, hypertrophic synovitis, vessel proliferation, inflammatory cell migration and, possibly, angiogenesis in pannus formation. These pathological changes, however, are not yet defined in the human model of chronic inflammation. The role of kinins and their interacting inflammatory mediators would soon start to clarify the detailed questions they revealed in clinical and experimental models of chronic inflammatory diseases. Several B1 and B2 receptor antagonists are being synthesized in an attempt to study the molecular functions of kinins in inflammatory processes, such as rheumatoid arthritis, periodontitis, inflammatory diseases of the gut and osteomyelitis. Future development of specific potent and stable B1 and B2 receptor antagonists or combined B1 and B2 antagonists with y-IFN might serve as a pharmacological basis for more effective treatment of joint inflammatory and related diseases.
Sharma
J N
JN
Department of Pharmacology, School of Medical Sciences, University Sains Malaysia, Kelantan.
Buchanan
W W
WW
D000595:Amino Acid Sequence; D001172:Arthritis, Rheumatoid / Q000378:metabolism*; D001920:Bradykinin / Q000378:metabolism*; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D007609:Kallidin / Q000378:metabolism; D007610:Kallikreins / Q000378:metabolism; D007705:Kinins / Q000378:metabolism*; D008969:Molecular Sequence Data
D018836:Inflammation Mediators; D007705:Kinins; D007609:Kallidin; D007610:Kallikreins; D001920:Bradykinin