Postburn monocytes are the major producers of TNF-alpha in the heterogeneous splenic macrophage population

Increased tumor necrosis factor (TNF)-alpha production by postburn splenic macrophages is well documented. Splenic macrophages are a heterogeneous population, and the effect of thermal injury on these subpopulations has not been documented. We examined the effects of scald injury on myeloid cells with the phenotype of red pulp, white pulp, and marginal zone monocyte/macrophages. We found that thermal injury greatly increased the number of splenocytes with the phenotype of white pulp monocytes. These cells were the major producers of TNF-alpha in the postburn spleen. Cells with the red pulp macrophage phenotype had an increased ability to make TNF-alpha after burn injury, but had only half the capacity to make TNF-alpha as did postburn monocytes. The postburn changes in TNF-alpha production correlated with an increased in vivo susceptibility to endotoxin. The increase in monocytes in the spleen from postburn days 1 to 10 correlated with an increasing ability of splenocytes to produce granulocyte colony-stimulating factor, monocyte chemoattractant protein 1, macrophage inflammatory protein 2, and macrophage inflammatory protein 1-alpha. These data suggest that the monocyte is a major source of inflammatory cytokines in the postburn spleen.