Interleukin-8 down-regulates the oxidative burst induced by tumor necrosis factor alpha in neutrophils adherent to...

Human neutrophils (5 x 10(4) incubated on fibronectin precoated wells released 2.83 +/- .25 nmoles of superoxide (0(2)-) (x +/- 1 SEM, n = 15) in response to 5.9 nM (100 ng/ml) Tumor Necrosis Factor Alpha (TNF). On the contrary, the 0(2)- production induced by interleukin-8 (IL-8) (doses ranging from 0.1 nM to 1 microM) was comparable to that of "resting" cells (< .6 nmoles/5 x 10(4) cells). IL-8 (100 nM) did not affect the TNF-dependent 0(2)- production when added with TNF at the beginning of the assay, but reduced it by approximately 80% when added with TNF on neutrophils previously incubated for 1 hour on fibronectin. As compared with IL-8, N-formyl-methionyl-leucyl-phenylalanine (FMLP, 100 nM) failed to suppress the TNF-triggering of the oxidative burst in neutrophils plated on fibronectin. The data suggest that the interaction of neutrophils with fibronectin uncovers the capacity of IL-8 to limit the cell response to TNF, without affecting the response to the combination of FMLP and TNF. Thus, although the chemotactic factors IL-8 and FMLP share the capacity of triggering the oxidative burst of neutrophils incubated in suspension, only IL-8 has the potential to down-regulate the responsiveness of fibronectin-adherent cells to TNF.