CXC chemokine redundancy ensures local neutrophil recruitment during acuteinflammation

Previous publications demonstrated that elevated systemic levels of interle ukin (IL)-8 decrease local neutrophil recruitment. We tested whether sustai ned, high plasma levels of IL-8 would prevent local inflammation after infl ammatory insults. Mice carrying the transgene for human IL-8 were separated on the basis of their plasma levels of IL-8 into IL-8-positive (plasma lev els >90 ng/ml) and IL-8-negative (IL-8 below detection). Presence of the IL -8 transgene did not improve survival or morbidity nor did it alter periton eal neutrophil recruitment induced by the cecal ligation and puncture model of sepsis. in an acute lung injury model created by intratracheal injectio n of acid, IL-8-positive mice showed no reduction in alveolar neutrophil re cruitment. There was no difference in the local recruitment of neutrophils when either thioglycollate or glycogen was injected intraperitoneally. We e xamined the chemotactic response to murine chemokines to test how neutrophi l recruitment occurs in the setting of elevated plasma IL-8 and found that neutrophils from both IL-8-positive and -negative mice respond equally well to recombinant KC or macrophage inflammatory protein (MEP)-2. We measured KC and MIP-2 in the peritoneum after thioglycollate injection and demonstra ted that IL-8-positive mice have significantly higher levels of the chemoki nes compared to the IL-8-negative mice. Antibody inhibition of KC and MIP-2 in the IL-8-positive mice significantly decreased peritoneal neutrophil re cruitment in response to thioglycollate, clarifying their important role in the local neutrophil recruitment. Our data demonstrate that despite the pr esence of high plasma levels of IL-8, neutrophils; may still be recruited t o sites of local inflammation because of chemokine redundancy.