Jn. Sharma et Ww. Buchanan, PATHOGENIC RESPONSES OF BRADYKININ SYSTEM IN CHRONIC INFLAMMATORY RHEUMATOID DISEASE, Experimental and toxicologic pathology, 46(6), 1994, pp. 421-433
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.