Document 0090
 DOCN  M9550090
 TI    [Analysis of host defense mechanism against mycobacterial infection and
       its application to therapy with biological response modifiers]
 DT    9505
 AU    Kawakami K; First Department of Internal Medicine, Faculty of Medicine,;
       University of the Ryukyus, Okinawa, Japan.
 SO    Kekkaku. 1994 Nov;69(11):719-23. Unique Identifier : AIDSLINE
       MED/95139538
 AB    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-gamma mRNA was induced
       in murine lungs after mycobacterial infection, and anti-IFN-gamma
       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 alpha beta 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-gamma significantly increased this population in lungs. Thus,
       IFN-gamma 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-gamma significantly reduced the number of the
       bacilli in lungs. Further, in an in vitro study with human lung
       macrophages, IFN-gamma enhanced the killing activity of macrophages
       against M. tuberculosis in a dose dependent manner, and suboptimal dose
       of 1 alpha, 25-dihydroxyvitamin D3 synergistically augmented the effect
       of IFN-gamma.
 DE    Animal  Biological Response Modifiers/*THERAPEUTIC USE  English Abstract
       Human  Interferon Type II/THERAPEUTIC USE  Mice  Mycobacterium
       Infections/*IMMUNOLOGY/THERAPY  JOURNAL ARTICLE  REVIEW  REVIEW,
       TUTORIAL

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