       Document 0137
 DOCN  M9550137
 TI    The role of TNF-alpha in T-cell-mediated inflammation depends on the
       Th1/Th2 cytokine balance.
 DT    9505
 AU    Hernandez-Pando R; Rook GA; Department of Pathology, Instituto Nacional
       de la Nutricion; Salvador Zubiran, Mexico DF.
 SO    Immunology. 1994 Aug;82(4):591-5. Unique Identifier : AIDSLINE
       MED/95137621
 AB    The role of tumour necrosis factor-alpha (TNF-alpha) in tuberculosis is
       paradoxical because although there is much evidence for a protective
       role, there is also evidence that it plays a part in the tissue damage
       that characterizes human disease. We have shown previously that
       TNF-alpha frequently induces necrosis when injected into sites
       undergoing delayed-type hypersensitivity (DTH) responses to
       mycobacterial antigen. This is dependent on CD4+ T cells. However the
       presence of this sensitivity to TNF-alpha-induced necrosis depended on
       the immunization protocol. We have tested the hypothesis that
       sensitivity to TNF-alpha depends on the cytokine profile of the induced
       T-cell response. All subcutaneous doses of mycobacterial immunogen used
       (10(7) to 10(9) organisms) primed spleen cells so that they secreted
       interferon-gamma (IFN-gamma) and interleukin-2 (IL-2) when cultured in
       vitro with soluble antigen. However priming for production of IL-4 was
       dose dependent as in other systems, and was produced at all times from 7
       to 30 days after immunization with 10(9) organisms. Time-course studies
       over 30 days showed that sensitivity to TNF-alpha was found in DTH sites
       of animals primed for IL-4 and IFN-gamma production, but not in animals
       primed only for the Th1 cytokines. We suggest therefore that the
       paradoxical role of TNF-alpha can be resolved. In 'pure' Th1 responses
       it may act as an additional macrophage-activating factor. In mixed Th1 +
       Th2 or Th0 responses it may cause tissue damage. This mixed pattern is
       characteristic of tuberculosis, and of the late stage of many chronic
       infections where elimination of the infecting organism is failing, and
       chronic tissue damage is seen.
 DE    Animal  Antigens, Bacterial/ADMINISTRATION & DOSAGE/*IMMUNOLOGY
       Cytokines/*BIOSYNTHESIS  Dose-Response Relationship, Immunologic
       Hypersensitivity, Delayed/IMMUNOLOGY  Immunization/METHODS  Interferon
       Type II/BIOSYNTHESIS  Interleukin-4/BIOSYNTHESIS  Kinetics  Mice  Mice,
       Inbred C57BL  Mycobacterium/*IMMUNOLOGY  Recombinant Proteins/IMMUNOLOGY
       Support, Non-U.S. Gov't  T-Lymphocytes, Helper-Inducer/*IMMUNOLOGY  Th1
       Cells/IMMUNOLOGY  Th2 Cells/IMMUNOLOGY  Tumor Necrosis
       Factor/*IMMUNOLOGY  JOURNAL ARTICLE

       SOURCE: National Library of Medicine.  NOTICE: This material may be
       protected by Copyright Law (Title 17, U.S.Code).

