A Therapeutic Trial of Experimental Tuberculosis with Gamma-Interferon in an Immunocompromised Mouse Model

Kazuyoshi Kawakami, Katsuji Teruya, Masaki Tohyama, Norifumi Kudeken, Atsushi Saito

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

It has been well documented that IFN-γ plays an important role in the host defense against Mycobacterium tuberculosis infection through activating macrophages to kill the organism. In the present study, we studied the effects of in vivo injection of monoclonal antibody against IFN-γ (anti-IFN-γ mAh) on the mycobacterial infection to confirm the role of this cytokine. The injection of anti-IFN-γ mAb suppressed the enhanced expression of MHC class II and ICAM-1 on pulmonary parenchymal macrophages induced by intravenous injection of Mycobacterium bovis BCG. The number of bacilli recovered from lung of mice treated with anti-IFN-γ mAb and injected with Mycobacterium tuberculosis H37Rv was significantly larger than that of the control infected mice. From these results, it was indicated that anti-IFN-γ mAb blocked the activities of endogenously synthesized IFN-γ, thus inhibited the activation of macrophages to kill the bacilli. Next, CD4+ T cell-depleted mice were prepared by injecting anti-CD4 mAb and used as immunocompromised animal. When infected with M. tuberculosis, the multiplication of the bacilli within the lungs of such immunocompromised mice was much more enhanced in comparison with the control mice with intact CD4+ T cells. Administration of IFN-γ significantly reduced the number of the bacilli in lung. Further, in an in vitro study with human lung macrophages, IFN-γ enhanced the killing activity of macrophages against M. tuberculosis in a dose dependent manner, and suboptimal dose of la, 25-dihydroxyvitamin D3 synergistically augmented the effect of IFN-γ These results suggest that an adjuvant therapy with IFN-γ may be hopeful in the treatment of tuberculosis caused by multi-drug resistant bacilli in immunocompromised patients.

Original languageEnglish
Pages (from-to)607-613
Number of pages7
JournalKekkaku
Volume69
Issue number10
DOIs
Publication statusPublished - 1994 Jan 1
Externally publishedYes

Keywords

  • 25-dihydroxyvitamin D
  • IFN-γ
  • Macrophage
  • Mice
  • Tuberculosis

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Infectious Diseases

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