Neutrophil infiltration as a crucial step for monocyte chemoattractant protein (MCP)-1 to attract monocytes in lipopolysaccharide-induced arthritis in rabbits

Objective and Design: To evaluate the mechanism whereby monocyte chemoattra ctant protein (MCP)-1 attracts monocytes in vivo. Subjects: New Zealand white rabbits (175 rabbits) were used. Treatment: LPS, MCP-1 or IL-8 was injected into knee joints. Antibodies aga inst various cytokines or IL-1 receptor antagonist were injected to neutral ize cytokine activities. Methods: The numbers of leukocyte populations, levels of cytokines in joint s were estimated. Results: Partial inhibition of neutrophil influx with anti-IL-8 IgG (10 mug ) suppressed LPS-induced macrophage influx by 43 +/- 8.5% (p<0.05) without affecting the MCP-I level. Intraarticular injection of MCP-1 (1-30 <mu>g) i nduced macrophage influx. The event was accompanied by a small number of ne utrophils in an early phase. Go-injection of IL-8 (1.0 mug) enhanced the MC P-1-induced macrophage infiltration (p<0.01). In neutrophil-depleted rabbit s, LPS failed to induce macrophage influx even though the MCP-1 level was m aintained, and macrophage influx following exogenously administered MCP-1 w as also dramatically inhibited. Conclusions: Early events associated with neutrophil infiltration appear to be important for MCP-1 to induce a later macrophage influx in LPS-arthriti s.