Investigation of the functional role played by the chemokine monocyte chemoattractant protein‐1 in interleukin‐1‐induced murine peritonitis

1 Intraperitoneal (i.p.) injection of murine recombinant IL‐1β (mrIL‐1β) produced a dose‐dependent (0.5–50 ng) and time‐related (0.5–2 h) secretion of murine monocyte chemoattractant protein‐1 (mMCP‐1; 3–4 ng per cavity) in the lavage fluids. MCP‐1 mRNA could also be detected in the cell pellets by reverse transcriptase‐polymerase chain reaction (RT‐PCR). 2 MCP‐1 levels were reduced by more than 90% by co‐administration of IL‐1 receptor antagonist (10 μg) ( n =6, P <0.05 ). In contrast, an IL‐1 mutant with low affinity for IL‐1 receptor type I, termed yIL‐1βΔ4 (50 ng), produced only a modest release of the chemokine. Treatment of mice with dexamethasone (DEX) (∼1 mg kg −1 s.c.) reduced mrIL‐1β‐induced mMCP‐1 gene expression (apparent total inhibition) and protein release in the lavage fluids (∼40% reduction; n =10; P <0.05). Drastic reductions in the numbers of residential macrophages or mast cells did not modify the levels of mMCP‐1 recovered in the lavage fluids. 3 Injection of mrIL‐1β produced neutrophil accumulation into the peritoneal cavities (maximal at 4 h with 1.42±0.15×10 6 cells per mouse). Co‐injection of a specific polyclonal antibody against mMCP‐1 reduced this process by more than 50% ( n =6; P <0.05). In conclusion, we studied the mechanisms leading to the specific release of the CC chemokine mMCP‐1 after in vivo administration of mrIL‐1β.British Journal of Pharmacology (1998) 125 , 319–326; doi: 10.1038/sj.bjp.0702071