In vivo effects of interferon-gamma and indomethacin on murine alveolar macrophage activity.
This study determined the effects of treatment with recombinant interferon-gamma (rIFN-gamma) and the cyclooxygenase inhibitor, indomethacin (INDO), on alveolar macrophage (AM) immune function in AKR/J mice. Bactericidal activity, interleukin 1 (IL1) synthesis and antigen presentation by AM were enhanced at 24 hr after a single intravenous injection with 5 X 10(4) U of rIFN-gamma. Concomitant treatment with 2 mg INDO/kg given subcutaneously did not further enhance the effects of a single injection of rIFN-gamma, even though the prostaglandin E2 (PGE2) concentrations in lung airways were reduced by 50%. These results suggest that the stimulatory effects of rIFN-gamma on AM are not altered by blocking potentially immunosuppressive cyclooxygenase metabolites such as PGE2 with INDO. Mice given three consecutive daily intravenous injections of 5 X 10(4) U of rIFN-gamma had suppressed AM bactericidal activity and IL1 synthesis, while PGE2 concentrations in the lungs were increased. Concomitant treatment with INDO prevented suppression of these AM functions and elevation of PGE2 concentrations in the lungs. Therefore, it appears that INDO can prevent suppression of AM activity induced by multiple injections of rIFN-gamma and this effect may be by blockage of PGE2 synthesis or other cyclooxygenase-derived products.
Stevens
M G
MG
Department of Veterinary Science, University of Idaho, Moscow 83843.
Exon
J H
JH
Olson
D P
DP
D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology; D004306:Dose-Response Relationship, Immunologic; D004334:Drug Administration Schedule; D004338:Drug Combinations; D007213:Indomethacin / Q000494:pharmacology*; D007275:Injections, Intravenous; D007371:Interferon-gamma / Q000494:pharmacology*; D008262:Macrophage Activation / Q000187:drug effects*; D008264:Macrophages / Q000276:immunology*; D008297:Male; D051379:Mice; D008806:Mice, Inbred AKR; D011650:Pulmonary Alveoli; D011994:Recombinant Proteins
D004338:Drug Combinations; D011994:Recombinant Proteins; D007371:Interferon-gamma; D007213:Indomethacin