kallidin and Arthritis--Rheumatoid

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.

Topics: Amino Acid Sequence; Arthritis, Rheumatoid; Bradykinin; Humans; Inflammation Mediators; Kallidin; Kallikreins; Kinins; Molecular Sequence Data

An enzyme-linked immunosorbent assay method is described for the measurement of kinin formation in synovial fluid from patients with rheumatoid and osteoarthritis (RA and OA). Basal kinin concentrations were less than 6 ng/ml in synovial fluid collected in the presence of inhibitors of kinin forming (kininogenase) and kinin metabolising (kininase) enzymes. During incubation of synovial fluid in the presence of kininase inhibitors alone, kinins were produced rapidly over the first 10 min, but production ceased completely within 30 min due to inhibition of the endogenous kininogenases; the rate of kinin generation during the early rapid phase correlated well with the plateau kinin concentration. Plateau kinin levels in synovial fluid from 15 patients with OA and RA ranged from 98 to 427 ng/ml, with a median value of 148 ng/ml. This study demonstrates clearly that synovial fluid from arthritis patients has the capacity to produce kinins. Although the number of patients was small, the amount of kinin generated in vitro varied over a wide range and a relationship between intra-articular kinin formation and clinical features may become apparent in a larger group of patients. The technique could also be used to investigate other biological systems in which a role has been proposed for kinins.

Topics: Arthritis, Rheumatoid; Binding, Competitive; Bradykinin; Carboxypeptidases; Cartilage; Cytochrome c Group; Enzyme-Linked Immunosorbent Assay; Humans; Hyaluronoglucosaminidase; Kallidin; Kallikreins; Kininogens; Kinins; Osteoarthritis; Synovial Fluid

Topics: Arthritis; Arthritis, Rheumatoid; Biological Assay; Bradykinin; Chemistry Techniques, Analytical; Eczema; Female; Humans; Hypertension; Kallidin; Kinins; Peptides; Pre-Eclampsia; Pregnancy; Rats; Urine; Uterus

Topics: Adult; Aged; Arthritis, Rheumatoid; Bradykinin; Humans; In Vitro Techniques; Kallidin; Male; Middle Aged; Urine