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 chemoattractant 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 against various cytokines or IL-1 receptor antagonist were injected to neutralize cytokine activities. Methods: The numbers of leukocyte populations, levels of cytokines in joints were estimated. Results: Partial inhibition of neutrophil influx with anti-IL-8 IgG (10 μg) suppressed LPS-induced macrophage influx by 43 ± 8.5% (p<0.05) without affecting the MCP-1 level. Intraarticular injection of MCP-1 (1-30 μg) induced macrophage influx. The event was accompanied by a small number of neutrophils in an early phase. Co-injection of IL-8 (1.0 μg) enhanced the MCP-1-induced macrophage infiltration (p<0.01). In neutrophil-depleted rabbits, LPS failed to induce macrophage influx even though the MCP-1 level was maintained, and macrophage influx following exogenously administered MCP-1 was 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-arthritis.