Tumor necrosis factor-alpha, interleukin-8 and chemotactic cytokines

There is little doubt that the high degree of communication observed during an immune response occurs via sophisticated cell-to-cell mediator circuits. The coordinate expression of specific signals are needed to orchestrate inflammation as the lesion is initiated, maintained, and finally resolved. Each of these phases can be viewed as a unique window of inflammation that is driven by a specific set of mediators. In this manuscript, we have developed the concept that cytokine-cytokine interactions play a prominent role in the elicitation of inflammatory cells. Our data demonstrate that the expression of chemotactic cytokines are both cell and stimulus specific. Interleukin-8, neutrophil chemotactic factor, can be synthesized by a variety of immune and non-immune cells, but the production is dependent upon an appropriate challenge. The production of monocyte chemotactic factor is much more cell restricted and appears to be generated in abundance by only non-immune cells (fibroblasts, endothelial cells, and epithelial cells). These data suggest that the recruitment of cells to a site of inflammation is dependent upon the expression of specific cytokines for both the induction and maintenance of the lesion.