The present knowledge of the inflammatory process and the inflammatory mediators.

Abstract

Endothelial damage, synovial oedema, fibrin deposition, polymorphonuclear cell (PMN) invasion, and mild lining cell hyperplasia characterize acute inflammatory arthritis. Later on, perivascular tissue is infiltrated by mononuclear cells. The early events are mediated by interactions between PMNs and endothelial cells. Both parts in the adhesion event are activated with multiple stimuli resulting in complex interactions of varying intensity and duration. Adhesion molecules present on the surface of PMNs (L-selectin) or induced by inflammatory stimuli (beta 2-integrins) mediate PMN adhesion to activated endothelium, which has counter receptors (E-selectin for L-selectin and ICAM-1 and ICAM-2 for beta 2-integrins). At the initial phase L-selectin initiates the rolling of PMNs on endothelial cells. Further stimuli result in a more prolonged adhesion between PMNs and endothelium. At the side of endothelium, induction of P-selectin and PAF by histamine, thrombin and LTC4 contribute to the acute rolling of PMNs on endothelial surface. Tumor necrosis factor (TNF), interleukin-1 (IL-1) and lipopolysaccharide activate endothelial cells to synthesize interleukin-8 (IL-8), a potent chemotactic and proadhesive mediator for PMNs, and further adhesion molecule (E-selectin), a mediator of long-term adhesion between PMN and endothelium. After adhesion and migration to the focus of inflammation, PMNs induce inflammation by aggregating, releasing hydrolyzing enzymes, generating lipid peroxidation products such as prostaglandins and LTB4, and oxygen derived free radicals. In studies on the pathogenesis of seronegative spondyloarthropathies, we have shown persistently aberrant PMN function evidenced by enhanced chemotaxis and high production of toxic oxygen derived free radicals by PMN.(ABSTRACT TRUNCATED AT 250 WORDS)