Intratracheal interferon-gamma augments pulmonary defenses in experimental legionellosis

Am J Respir Crit Care Med. 1994 Jan;149(1):50-8. doi: 10.1164/ajrccm.149.1.8111597.

Abstract

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.

Publication types

  • Comparative Study
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Autoantigens / analysis
  • Bronchoalveolar Lavage Fluid / chemistry
  • Cortisone / administration & dosage
  • Cortisone / analogs & derivatives
  • Dose-Response Relationship, Drug
  • Gene Expression Regulation, Bacterial / drug effects
  • Immunosuppression
  • Injections
  • Injections, Intraperitoneal
  • Interferon-gamma / immunology
  • Interferon-gamma / therapeutic use*
  • Legionella pneumophila / drug effects*
  • Legionella pneumophila / genetics
  • Legionella pneumophila / metabolism
  • Legionnaires' Disease / immunology
  • Legionnaires' Disease / therapy*
  • Lymphocyte Activation / drug effects
  • Macrophage Activation / drug effects
  • Macrophages, Alveolar / chemistry
  • Male
  • Mucociliary Clearance / drug effects
  • Rats
  • Rats, Sprague-Dawley
  • Recombinant Proteins
  • Ribonucleoproteins / analysis
  • Spleen / cytology
  • Trachea
  • Transcription Factors / analysis

Substances

  • Autoantigens
  • Recombinant Proteins
  • Ribonucleoproteins
  • SS-B antigen
  • Transcription Factors
  • Interferon-gamma
  • Cortisone