Ms. Mulligan et al., INHIBITION OF LUNG INFLAMMATORY REACTIONS IN RATS BY AN ANTI-HUMAN IL-8 ANTIBODY, The Journal of immunology, 150(12), 1993, pp. 5585-5595
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.