Effects of aminoguanidine on latent murine tuberculosis

Joanne L. Flynn, Charles A. Scanga, Kathryn E. Tanaka, John Chan

Research output: Contribution to journalArticle

165 Citations (Scopus)

Abstract

A unique feature of Mycobacterium tuberculosis is its ability to establish latent infection in the human host, which can reactivate to cause disease years later. In the present study, the mechanisms involved in the control of latent tuberculosis infection were examined using two murine experimental tuberculosis models. Analysis of the model involving infection of mice with a relatively low inoculum of the virulent Erdman strain of M. tuberculosis indicated that in vivo inhibition of reactive nitrogen intermediate (RNI) production by the nitric oxide synthase inhibitor aminoguanidine resulted in reactivation. This reactivation was evidence by hepatosplenomegaly, a robust tissue granulomatous reaction, and increased bacillary load. IFN-γ, TNF-α, and inducible nitric oxide synthase were all expressed throughout the latent phase of infection. Reactivation of latent tuberculosis infection by aminoguanidine treatment was confirmed using a second murine tuberculosis model based on treatment with antimycobacterial drugs. Results obtained using this drug-based model also suggested the existence of an RNI-independent antimycobacterial mechanism(s) operative in the latent phase of infection. Together, these data suggest that both RNI- dependent and -independent mechanisms contribute to the prevention of tuberculous reactivation.

Original languageEnglish (US)
Pages (from-to)1796-1803
Number of pages8
JournalJournal of Immunology
Volume160
Issue number4
StatePublished - Feb 15 1998

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Latent Tuberculosis
Nitrogen
Infection
Mycobacterium tuberculosis
Reactive Inhibition
Tuberculosis
Aptitude
Nitric Oxide Synthase Type II
Nitric Oxide Synthase
Pharmaceutical Preparations
Theoretical Models
pimagedine

ASJC Scopus subject areas

  • Immunology

Cite this

Flynn, J. L., Scanga, C. A., Tanaka, K. E., & Chan, J. (1998). Effects of aminoguanidine on latent murine tuberculosis. Journal of Immunology, 160(4), 1796-1803.

Effects of aminoguanidine on latent murine tuberculosis. / Flynn, Joanne L.; Scanga, Charles A.; Tanaka, Kathryn E.; Chan, John.

In: Journal of Immunology, Vol. 160, No. 4, 15.02.1998, p. 1796-1803.

Research output: Contribution to journalArticle

Flynn, JL, Scanga, CA, Tanaka, KE & Chan, J 1998, 'Effects of aminoguanidine on latent murine tuberculosis', Journal of Immunology, vol. 160, no. 4, pp. 1796-1803.
Flynn JL, Scanga CA, Tanaka KE, Chan J. Effects of aminoguanidine on latent murine tuberculosis. Journal of Immunology. 1998 Feb 15;160(4):1796-1803.
Flynn, Joanne L. ; Scanga, Charles A. ; Tanaka, Kathryn E. ; Chan, John. / Effects of aminoguanidine on latent murine tuberculosis. In: Journal of Immunology. 1998 ; Vol. 160, No. 4. pp. 1796-1803.
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