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Infection and Immunity, May 2004, p. 2976-2988, Vol. 72, No. 5
0019-9567/04/$08.00+0     DOI: 10.1128/IAI.72.5.2976-2988.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Interleukin-12 Therapy Reduces the Number of Immune Cells and Pathology in Lungs of Mice Infected with Mycobacterium tuberculosis

Dawn Nolt1 and JoAnne L. Flynn2*

Division of Allergy, Immunology, and Infectious Diseases, Children's Hospital of Pittsburgh,1 Department of Molecular Genetics and Biochemistry, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 152612

Received 11 December 2003/ Returned for modification 19 January 2004/ Accepted 6 February 2004

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.

* Corresponding author. Mailing address: Department of Molecular Genetics and Biochemistry, 200 Lothrop St., W1157 Biomedical Science Tower, University of Pittsburgh School of Medicine, Pittsburgh, PA 15216. Phone: (412) 624 7743. Fax: (412) 648 3394. E-mail: joanne{at}pitt.edu.

Editor: J. B. Bliska

Infection and Immunity, May 2004, p. 2976-2988, Vol. 72, No. 5
0019-9567/04/$08.00+0     DOI: 10.1128/IAI.72.5.2976-2988.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



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