Essential involvement of interleukin-8 in neutrophil recruitment in rabbits with acute experimental arthritis induced by lipopolysaccharide and interleukin-1.

Rheumatoid arthritis and related inflammatory joint diseases are characterized by massive infiltration of polymorphonuclear cells (PMN) into inflamed joints. Interleukin-8 (IL-8) has recently been identified as a leukocyte chemotactic and activating factor produced by activated tissue cells as well as monocytes/macrophages. Examination was made of the involvement of IL-8 in acute arthritis induced by injecting lipopolysaccharide (LPS) or interleukin-1 alpha (IL-1 alpha) into the joints of rabbits. The neutralizing antibody to rabbit IL-8 blocked almost completely the infiltration of PMN into the joints and provided protection from damage to tissue in the early phase of inflammation induced by LPS or IL-1 alpha. Mononuclear cell infiltration observed later was not inhibited by this antibody. This is the first paper to clearly demonstrate that IL-8 is an essential and major mediator determining whether PMN infiltration will occur in the early phase of experimental acute arthritis.