Analysis of host defense mechanism against mycobacterial infection and its application to therapy with biological response modifiers

Research output: Contribution to journalArticle

Abstract

Recently, tuberculosis have been increasing among the immunocompromised patients. In patients with acquired immunodeficiency syndrome (AIDS), multi-drug resistant mycobacteria are often detected, which make the therapy difficult. In these patients, chemotherapy alone is often insufficient and some treatment to augment their host defense activity has been desired. Therefore, to know the host defense mechanism against mycobacterial infection will be helpful to develop an adjuvant therapy for intractable tuberculosis. In this study, IFN-γ mRNA was indeed in murine lungs after mycobacterial infection, and anti-IFN-γ monoclonal antibody (mAb) prevented the activation of pulmonary intraparenchymal macrophages by M. bovis BCG and the elimination of M. tuberculosis from lungs. In addition, this mAb inhibited the activation of Mac1+CD4-CD8- T cells bearing αβ antigen receptor by BCG, which were found in murine lungs and might be involved in the host defense mechanism against mycobacterial infection, and administration of IFN-γ significantly increased this population in lungs. Thus, IFN-γ was suggested to be a candidate cytokine for the treatment of intractable tuberculosis. Next, CD4+ T cell depleted mice were prepared by injecting anti-CD4 mAb and used as an immunocompromised model. 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 lungs. 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 1α, 25-dihydroxyvitamin D3 synergistically augmented the effect of IFN-γ. Recenty, it has been reported that IFN-γ treatment was attempted for some diseases such as atypical mycobacteriosis, lepromatous leprosy, chronic granulomatous disease, adult T cell leukemia and atopic dermatitis without any serious side effects. Together, these results suggest that an adjuvant therapy with IFN-γ is hopeful in the treatment of tuberculosis caused by multi-drug resistant bacilli in immunocompromised patients.

Original languageEnglish
Pages (from-to)719-723
Number of pages5
JournalKekkaku
Volume69
Issue number11
Publication statusPublished - 1994 Jan 1
Externally publishedYes

Keywords

  • 1a,25-dihydroxyvitamin D
  • BRM
  • IFN-γ
  • Mac1CD4CD8 T cells bearing αβ antigen receptor
  • tuberculosis

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Infectious Diseases

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