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

摘要

class="enumerated" style="list-style-type:decimal">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).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.Injection of mrIL-1β produced neutrophil accumulation into the peritoneal cavities (maximal at 4 h with 1.42±0.15×10⁶ 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.