Lower expression of Th1-related cytokines and inducible nitric oxide synthase in mice with streptozotocin-induced diabetes mellitus infected with Mycobacterium tuberculosis

S. Yamashiro, Kazuyoshi Kawakami, K. Uezu, T. Kinjo, K. Miyagi, K. Nakamura, A. Saito

Research output: Contribution to journalArticlepeer-review

78 Citations (Scopus)

Abstract

Diabetes mellitus is an important predisposing factor for tuberculosis. The aim of this study was to investigate the mechanism underlying this association using a murine model. Mice with streptozotocin-induced diabetes mellitus were prone to Mycobacterium tuberculosis infection, as indicated by increased numbers of live bacteria in lung, liver and spleen. In diabetic mice, the levels of IL-12 and IFN-γ in the lung, liver and spleen were lower than those in control animals on day 14 postinfection, while the opposite was true for IL-4 levels in the lung and liver. The expression pattern of inducible nitric oxide synthase (iNOS), in the two mice types was as for IL-12 and IFN-γ. In addition, peritoneal exudate cells obtained from diabetic mice produced lower amounts of IL-12 and NO than those from control mice, when stimulated in vitro with M. bovis BCG. Spleen cells from diabetic mice infected with M. tuberculosis produced a significantly lower amount of IFN-γ upon restimulation with purified protein derivatives (PPD) than those from infected nondiabetic mice. Interestingly, addition of high glucose levels (33 mM) to the cultures of PPD-restimulated spleen cells reduced the synthesis of IFN-γ only in diabetic mice, and not in nondiabetic mice. Finally, control of blood glucose levels by insulin therapy resulted in improvement of the impaired host protection and Th1-related cytokine synthesis. Our results suggest that the reduced production of Th1-related cytokines and NO account for the hampered host defense against M. tuberculosis infection under diabetic conditions.

Original languageEnglish
Pages (from-to)57-64
Number of pages8
JournalClinical and Experimental Immunology
Volume139
Issue number1
DOIs
Publication statusPublished - 2005 Jan
Externally publishedYes

Keywords

  • Diabetes mellitus
  • IFN-γ
  • IL-12
  • Mycobacterium tuberculosis
  • Nitric oxide

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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