Intratracheal interferon-gamma augments pulmonary defenses in experimental legionellosis.
To study the effects of recombinant interferon-gamma (IFN-gamma) on pulmonary defenses in vivo, we measured Ia antigen expression by alveolar macrophages and whole-lung clearance of inhaled Legionella pneumophila in normal and corticosteroid-treated rats. We found that Ia antigen was expressed by 7, 29, 50, and 65% of alveolar macrophages harvested from normal rats 24 h after intratracheal administration of 0, 10(3), 10(4), or 10(5) U of IFN-gamma, respectively, and by 76% of alveolar macrophages harvested from corticosteroid-treated rats given 10(5) U of IFN-gamma. Corticosteroid-treated rats exhibited a marked impairment in the clearance of inhaled L. pneumophila, associated with diminished release of IFN-gamma by antigen-stimulated splenocytes and blunted up-regulation of Ia antigen by alveolar-exudate macrophages. Daily intratracheal injections of IFN-gamma starting 1 day before or 1 day after infection had little effect on bacterial clearance in normal rats but markedly reduced the intrapulmonary replication of L. pneumophila and the number of bronchoalveolar neutrophils in corticosteroid-treated animals. Intraperitoneally administered IFN-gamma had no effect on Ia expression by alveolar macrophages or on bacterial clearance. IFN-gamma may be useful in the treatment of intracellular infections when targeted to the site of infection in immunosuppressed hosts.
Skerrett
S J
SJ
Medical Research Service, Veterans Affairs Medical Center, Seattle, WA 98108.
Martin
T R
TR
D000818:Animals; D001324:Autoantigens / Q000032:analysis; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D003348:Cortisone / Q000008:administration & dosage / Q000031:analogs & derivatives; D004305:Dose-Response Relationship, Drug; D015964:Gene Expression Regulation, Bacterial / Q000187:drug effects; D007165:Immunosuppression Therapy; D007267:Injections; D007274:Injections, Intraperitoneal; D007371:Interferon-gamma / Q000276:immunology / Q000627:therapeutic use*; D016952:Legionella pneumophila / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D007877:Legionnaires' Disease / Q000276:immunology / Q000628:therapy*; D008213:Lymphocyte Activation / Q000187:drug effects; D008262:Macrophage Activation / Q000187:drug effects; D016676:Macrophages, Alveolar / Q000737:chemistry; D008297:Male; D009079:Mucociliary Clearance / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins; D012261:Ribonucleoproteins / Q000032:analysis; D013154:Spleen / Q000166:cytology; D014132:Trachea; D014157:Transcription Factors / Q000032:analysis; D000097585:SS-B Antigen
D001324:Autoantigens; D003348:Cortisone; D007371:Interferon-gamma; D011994:Recombinant Proteins; D012261:Ribonucleoproteins; D014157:Transcription Factors; D000097585:SS-B Antigen