Document 0375
 DOCN  M9610375
 TI    Cytokine interactions in human immunodeficiency virus-infected
       individuals: roles of interleukin (IL)-2, IL-12, and IL-15.
 DT    9601
 AU    Seder RA; Grabstein KH; Berzofsky JA; McDyer JF; National Institute of
       Allergy and Infectious Diseases, National; Institutes of Health,
       Bethesda, Maryland 20892, USA.
 SO    J Exp Med. 1995 Oct 1;182(4):1067-77. Unique Identifier : AIDSLINE
       MED/96018806
 AB    Cytokines have been shown to be powerful regulators of the immune
       response. In this study, we analyze the effect that the newly recognized
       cytokine interleukin (IL)-15 has on proliferation and cytokine induction
       using peripheral blood mononuclear cells (PBMCs) and purified CD4+ T
       cells from patients infected with human immunodeficiency virus (HIV) who
       are at various stages in their disease. We observed that IL-15 enhances
       the proliferative response in a dose-dependent manner from PBMCs of
       HIV-infected individuals when stimulated by polyclonal mitogen, tetanus
       toxoid, or HIV-specific antigen. The effects of exogenous IL-15 are
       substantially diminished by adding a neutralizing antibody to the beta
       chain of the IL-2 receptor. Moreover, the ability of IL-15 to increase
       proliferation is enhanced by the presence of endogenous IL-2 produced in
       the cultures. The effect that exogenous IL-15 had on IL-2, IL-4, and
       interferon (IFN)-gamma induction from PBMC's or CD4+ T cells in response
       to mitogen or tetanus toxoid was also examined. This was compared to the
       effect that exogenous IL-2 and IL-12 had under the same conditions.
       Addition of IL-2 or IL-15 to short-term in vitro cultures of either
       PBMCs or CD4+ T cells had little effect on IL-2, IL-4, or IFN-gamma
       production. By contrast, IL-12 caused substantial enhancement of both
       IL-2 and IFN-gamma production from these cultures. The role that
       endogenous cytokines have on IFN-gamma induction was also studied.
       Addition of a neutralizing antibody to the alpha chain of the IL-2
       receptor or IL-12 to antigen stimulated cultures caused a striking
       decrease in IFN-gamma production. Neutralization of endogenous IL-15
       also resulted in diminished IFN-gamma production from cultures
       stimulated with mitogen. IL-4 and IFN-gamma protein production by PBMCs
       and CD4+ T cells stimulated with mitogen was assessed to see if we could
       detect a specific bias of cytokine production. Small amounts of IL-4
       were detected from CD4+ T cells but not PBMCs from most individuals
       tested. IFN-gamma and IL-2, however, were also produced from these same
       cultures. These results further elucidate the mechanism of cytokine
       regulation in HIV-infected individuals, and they provide evidence that
       IL-15 may be a useful immune modulator.
 DE    Comparative Study  CD4-Positive T-Lymphocytes/IMMUNOLOGY  Drug
       Interactions  Human  HIV Antigens/PHARMACOLOGY  HIV
       Infections/*IMMUNOLOGY  Interferon Type II/*BIOSYNTHESIS
       Interleukin-12/PHARMACOLOGY  Interleukin-2/BIOSYNTHESIS/PHARMACOLOGY
       Interleukins/*PHARMACOLOGY  Leukocytes, Mononuclear/*IMMUNOLOGY
       Lymphocyte Transformation/*DRUG EFFECTS  Mitogens/PHARMACOLOGY
       Receptors, Interleukin-2/IMMUNOLOGY  JOURNAL ARTICLE

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