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 inflammatory 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 models of lung injury, IL-4 and IL-10 were individually coinstilled into the airways with the IgG or IgA antibodies, whereas the Ag were injected intravenously. Injury was quantitated by increases in permeability (leakage of 125I-BSA) and by hemorrhage (extravasation of 51Cr-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 protective 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 protective effects of IL-4 and IL-10 were associated with profound reductions of TNF-alpha in the BAL fluids and complete inhibition in the up-regulation of pulmonary vascular ICAM-1. In the IgA immune complex model of lung injury IL-4 had no protective effects, whereas IL-10 was highly protective. These protective effects correlated with diminished retrieval of alveolar macrophages in BAL fluids. These data suggest that IL-4 and IL-10 have significant protective effects in lung inflammatory injury, presumably achieving these effects by various mechanisms.
Mulligan
M S
MS
Department of Pathology, University of Michigan, Ann Arbor 48109.
Jones
M L
ML
Vaporciyan
A A
AA
Howard
M C
MC
Ward
P A
PA
D000818:Animals; D000936:Antigen-Antibody Complex / Q000276:immunology*; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology; D015815:Cell Adhesion Molecules / Q000032:analysis; D007070:Immunoglobulin A / Q000276:immunology; D007074:Immunoglobulin G / Q000276:immunology; D018799:Intercellular Adhesion Molecule-1; D016753:Interleukin-10 / Q000494:pharmacology*; D015847:Interleukin-4 / Q000494:pharmacology*; D008168:Lung / Q000737:chemistry / Q000187:drug effects / Q000473:pathology; D008297:Male; D011014:Pneumonia / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D011817:Rabbits; D051381:Rats; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
D000936:Antigen-Antibody Complex; D015815:Cell Adhesion Molecules; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1; D016753:Interleukin-10; D015847:Interleukin-4