Combination of IL-8 plus TNF alpha induces additive neutrophil migration.

We have previously reported that TNF alpha's ability to induce neutrophil transendothelial and transepithelial migration was largely dependent on the generation of IL-8 by the endothelial or pulmonary epithelial cells. To further explore the interrelationship of IL-8 with TNF alpha, we examined the migration of human neutrophils through noncellular barriers in response to these cytokines alone or in combination. We directly compared neutrophil migration through 3 microns-pore size polycarbonate Transwell filters in response to 10 nM TNF alpha or either 10 nM TNF alpha or buffer plus 10(-8) to 10(-11) M IL-8. We found that the combination of TNF alpha and IL-8 induced neutrophil migration that was generally additive, and sometimes synergistic, to that of either agent alone. In conclusion, these data support the role of cytokine networking in inducing neutrophil-rich lung inflammatory responses.