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Appearance of Monocyte Chemoattractant Protein 1 (MCP-1) Early After Thermal Injury: Role in the Subsequent Development of Burn-Associated Type 2 T-Cell Responses

ObjectiveTo determine whether monocyte chemoattractant protein-1 (MCP-1), which initiates subsequent development of burn-associated type 2 T cells, is produced in mice early after thermal injury. Summary Background DataA predominance of type 2 T-cell responses is commonly observed in animals and patients with severe thermal injuries. Burn-associated type 2 T cells have been identified as the cells responsible for the increased susceptibility of thermally injured mice to infections with herpes simplex virus type 1 and Candida albicans. Recently, the necessity of MCP-1 for the generation of type 2 T cells was shown in MCP-1 knockout mice. MCP-1 may have an important role in the increased susceptibility of thermally injured mice to various intracellular opportunistic pathogens. MethodsThe production of MCP-1 in sera or in cultures of various cells prepared from thermally injured mice was measured. Dual-chamber transwell cultures were performed to determine the influence of MCP-1-producing cells on the generation of burn-associated type 2 T cells. ResultsWithout any stimulation, splenic macrophages from mice (1/2D-M&phgr;) produced MCP-1 into their culture fluids 12 hours after thermal injury. Interleukin-4 was detected in culture fluids of splenic T cells from normal mice cultured with 1/2D-M&phgr; in a dual-chamber transwell system; however, this cytokine was not produced by normal T cells cultured with normal macrophages in the transwells. Also, normal T cells cultured with 1/2D-M&phgr; did not produce interleukin-4 when transwell cultures were performed in the presence of anti-MCP-1 monoclonal antibody. Further, normal T cells directly stimulated with MCP-1 produced interleukin-4 into their culture fluids. Normal T cells, cultured with 1/2D-M&phgr; for 24 hours in the transwells and recultured with fresh medium for an additional 7 days, produced interleukin-10 (but not interferon-&ggr;) and expressed ST2L mRNA (but not interleukin-12 receptor &bgr;2 chain) when they were stimulated with anti-CD3 monoclonal antibody. ConclusionsResults indicate that MCP-1 is produced in mice within 1 day of thermal injury, and the subsequent development of burn-associated type 2 T-cell responses may be triggered by MCP-1 produced early after thermal injury.