       Document 0471
 DOCN  M9620471
 TI    Interleukin 12 inhibits antigen-induced airway hyperresponsiveness,
       inflammation, and Th2 cytokine expression in mice.
 DT    9602
 AU    Gavett SH; O'Hearn DJ; Li X; Huang SK; Finkelman FD; Wills-Karp M;
       Department of Environmental Health Sciences, Johns Hopkins; University,
       Baltimore, Maryland 21205, USA.
 SO    J Exp Med. 1995 Nov 1;182(5):1527-36. Unique Identifier : AIDSLINE
       MED/96042149
 AB    Allergic asthma is characterized by airway hyperresponsiveness and
       pulmonary eosinophilia, and may be mediated by T helper (Th) lymphocytes
       expressing a Th2 cytokine pattern. Interleukin (IL) 12 suppresses the
       expression of Th2 cytokines and their associated responses, including
       eosinophilia, serum immunoglobulin E, and mucosal mastocytosis. We have
       previously shown in a murine model that antigen-induced increases in
       airway hyperresponsiveness and pulmonary eosinophilia are CD4+ T cell
       dependent. We used this model to determine the ability of IL-12 to
       prevent antigen-induced increases in airway hyperresponsiveness,
       bronchoalveolar lavage (BAL) eosinophils, and lung Th2 cytokine
       expression. Sensitized A/J mice developed airway hyperresponsiveness and
       increased numbers of BAL eosinophils and other inflammatory cells after
       single or repeated intratracheal challenges with sheep red blood cell
       antigen. Pulmonary mRNA and protein levels of the Th2 cytokines IL-4 and
       IL-5 were increased after antigen challenge. Administration of IL-12 (1
       microgram/d x 5 d) at the time of a single antigen challenge abolished
       the airway hyperresponsiveness and pulmonary eosinophilia and promoted
       an increase in interferon (IFN) gamma and decreases in IL-4 and IL-5
       expression. The effects of IL-12 were partially dependent on IFN-gamma,
       because concurrent treatment with IL-12 and anti-IFN-gamma monoclonal
       antibody partially reversed the inhibition of airway hyperresponsiveness
       and eosinophilia by IL-12. Treatment of mice with IL-12 at the time of a
       second antigen challenge also prevented airway hyperresponsiveness and
       significantly reduced numbers of BAL inflammatory cells, reflecting the
       ability of IL-12 to inhibit responses associated with ongoing
       antigen-induced pulmonary inflammation. These data show that
       antigen-induced airway hyperresponsiveness and inflammation can be
       blocked by IL-12, which suppresses Th2 cytokine expression. Local
       administration of IL-12 may provide a novel immunotherapy for the
       treatment of pulmonary allergic disorders such as atopic asthma.
 DE    Animal  Antigens/IMMUNOLOGY/TOXICITY  Asthma  Biological Response
       Modifiers/PHARMACOLOGY/*THERAPEUTIC USE  Bronchial
       Hyperreactivity/IMMUNOLOGY/*PREVENTION & CONTROL  Bronchoalveolar Lavage
       Fluid/CYTOLOGY  Disease Models, Animal
       Eosinophilia/IMMUNOLOGY/*PREVENTION & CONTROL  Erythrocytes/IMMUNOLOGY
       Gene Expression Regulation/*DRUG EFFECTS  Inflammation  Interferon Type
       II/PHYSIOLOGY  Interleukin-12/PHARMACOLOGY/*THERAPEUTIC USE
       Interleukin-4/*BIOSYNTHESIS/GENETICS/SECRETION
       Interleukin-5/*BIOSYNTHESIS/GENETICS/SECRETION
       Lung/*IMMUNOLOGY/METABOLISM/PATHOLOGY  Male  Mice  Mice, Inbred A
       Respiratory Hypersensitivity/IMMUNOLOGY/*THERAPY  Sheep/BLOOD  Support,
       U.S. Gov't, Non-P.H.S.  Support, U.S. Gov't, P.H.S.  Th2
       Cells/*SECRETION  JOURNAL ARTICLE

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

