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.

journal_name

Infect Immun

journal_title

Infection and immunity

authors

Nolt D,Flynn JL

doi

10.1128/iai.72.5.2976-2988.2004

keywords:

subject

Has Abstract

pub_date

2004-05-01 00:00:00

pages

2976-88

issue

5

eissn

0019-9567

issn

1098-5522

journal_volume

72

pub_type

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