PROTECTIVE EFFECTS OF IL-4 AND IL-10 AGAINST IMMUNE COMPLEX-INDUCED LUNG INJURY

Recombinant murine IL-4 and IL-10 have been used in two models of infl ammatory lung injury in rats after intrapulmonary deposition of IgG or IgA immune complexes. These models have contrasting requirements for cytokines, phagocytic cells, and adhesion molecules. In these two mode ls of lung injury, IL-4 and IL-10 were individually coinstilled into t he airways with the IgG or IgA antibodies, whereas the Ag were injecte d intravenously. Injury was quantitated by increases in permeability ( leakage of I-125-BSA) and by hemorrhage (extravasation of Cr-51-RBC). In the model of IgG immune complex-induced lung injury, IL-4 and IL-10 were each highly protective when given in nanogram amounts. These pro tective effects were dose dependent. IL-4 and IL-10 caused substantial reductions in lung content of myeloperoxidase and parallel reductions in neutrophil content in bronchoalveolar lavage (BAL) fluids. The pro tective effects of IL-4 and IL-10 were associated with profound reduct ions of TNF-alpha in the BAL fluids and complete inhibition in the up- regulation of pulmonary vascular ICAM-1. In the IgA immune complex mod el of lung injury IL-4 had no protective effects, whereas IL-10 was hi ghly protective. These protective effects correlated with diminished r etrieval of alveolar macrophages in BAL fluids. These data suggest tha t IL-4 and IL-10 have significant protective effects in lung inflammat ory injury, presumably achieving these effects by various mechanisms.