INHIBITION OF LUNG INFLAMMATORY REACTIONS IN RATS BY AN ANTI-HUMAN IL-8 ANTIBODY

IL-8 belongs to the family of chemotactic cytokines and may play an im portant role in the inflammatory response. In the current studies, a m urine mAb (DM/C7) to human rIL-8 was found to have protective effects in inflammatory lung injury in rats. DM/C7 was nonreactive with the ra t cytokine-induced neutrophil chemoattractant peptide. In vivo, DM/C7 blocked the glycogen-induced accumulation of neutrophils in rats and w as highly protective against lung and dermal vascular injury after dep osition of IgG immune complexes. The latter model of injury has recent ly been shown to be E-selectin dependent. The protective effects of DM /C7 correlated with reduced tissue accumulation of neutrophils, as mea sured by myeloperoxidase content. DM/C7 reacted with an epitope expres sed by TNF-alpha-stimulated rat pulmonary artery endothelial cells and with the pulmonary vascular endothelium after intrapulmonary depositi on of IgG immune complexes. In the model of IgG immune complex-induced lung injury, the protective effects of DM/C7 were abolished by prior absorption of the antibody with human rIL-8. Polyclonal antibody to cy tokine-induced neutrophil chemoattractant peptide failed to protect ag ainst IgG immune complex-induced vascular injury even though this anti body blocked the in vitro chemotactic activity of cytokine-induced neu trophil chemoattractant. In the model of rapidly developing lung injur y due to systemic activation of C after infusion of cobra venom factor , DM/C7 was not protective. As well, in the neutrophil-independent mod el of IgA immune complex-induced lung injury, treatment with DM/C7 was not protective. These data indicate that in inflammatory lung injury that is linked to E-selectin-dependent recruitment of neutrophils in r ats, antibody to human IL-8 also blocks recruitment of neutrophils and thereby affords protection against lung injury. The data suggest the presence of an IL-8-like product in this model of lung injury.