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

We have previously reported that TNF alpha's ability to induce neutrophil t ransendothelial and transepithelial migration was largely dependent on the generation of IL-8 by the endothelial or pulmonary epithelial cells. To fur ther 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 mi gration through 3 mu m-pore size polycarbonate Transwell filters in respons e 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 ne utrophil migration that was generally additive, and sometimes synergistic, To that of either agent alone. In conclusion, these data support the role o f cytokine networking in inducing neutrophil-rich lung inflammatory respons es.