title: Interleukin-12 therapy reduces the number of immune cells and pathology in lungs of mice infected with Mycobacterium tuberculosis.
abstract: Alternate modalities for the treatment of Mycobacterium tuberculosis are needed due to the rise in numbers of immunosuppressed individuals at risk for serious disease and the increasing prevalence of multidrug-resistant isolates. Interleukin-12 (IL-12) has been shown to improve immune responses against M. tuberculosis infection in both humans and mice. Previous studies using high-dose IL-12 in various disease models reported a paradoxical immunosuppression. We demonstrate here that exogenous administration of IL-12 for 8 weeks after an aerosolized low dose of M. tuberculosis results in increased survival and decreased pulmonary bacterial loads for CD4-T-cell-deficient mice, most likely due to an early increase in gamma interferon. IL-12 treatment did not impair or enhance the ability of the wild-type mice to control infection, as measured by bacterial numbers. Two novel findings are reported here regarding exogenous IL-12 therapy for M. tuberculosis infections: (i). IL-12 treatment resulted in decreased numbers of immune cells and reduced frequencies of lymphocytes (CD8(+), CD4(+), and NK cells) in the lungs of infected mice and (ii). IL-12 therapy reduced the pathology of M. tuberculosis-infected lungs, as granulomas were smaller and less numerous. These studies support an immunoregulatory role for IL-12 in tuberculosis.
authors.affiliation: Division of Allergy, Immunology, and Infectious Diseases, Children's Hospital of Pittsburgh, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15261, USA.
authors.forename: Dawn
authors.initials: D
authors.lastname: Nolt
authors.forename: JoAnne L
authors.initials: JL
authors.lastname: Flynn
mesh_terms: D000276:Adjuvants, Immunologic / Q000627:therapeutic use; D000818:Animals; D015704:CD4 Antigens / Q000235:genetics / Q000378:metabolism; D006099:Granuloma / Q000473:pathology; D006801:Humans; D007249:Inflammation / Q000473:pathology; D007371:Interferon-gamma / Q000096:biosynthesis; D018664:Interleukin-12 / Q000627:therapeutic use*; D007694:Killer Cells, Natural / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D008168:Lung / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D008213:Lymphocyte Activation / Q000187:drug effects; D018655:Lymphocyte Count; D016131:Lymphocyte Subsets / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011994:Recombinant Proteins / Q000627:therapeutic use; D016176:T-Lymphocyte Subsets / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D014397:Tuberculosis, Pulmonary / Q000188:drug therapy* / Q000276:immunology* / Q000473:pathology
chemical_list: D000276:Adjuvants, Immunologic; D015704:CD4 Antigens; D011994:Recombinant Proteins; D018664:Interleukin-12; D007371:Interferon-gamma