       Document 0112
 DOCN  M9620112
 TI    In vitro cytokine treatment of B cell defects in HIV-infected hemophilia
       patients.
 DT    9602
 AU    Weimer R; Zipperle S; Daniel V; Opelz G; Department of Transplantation
       Immunology, University of; Heidelberg, Germany.
 SO    Vox Sang. 1995;69(1):27-37. Unique Identifier : AIDSLINE MED/96078298
 AB    HIV-infected patients exhibit defects in B cell differentiation and in
       the IL-6 response of B cells, in association with autoantibody formation
       against T cells. These autoantibodies have been implicated as important
       factors in the development of immunodeficiency disease. As the
       restoration of defective B cell responses might prevent autoantibody
       formation and the resulting immunosuppression, we studied whether in
       vitro treatment with recombinant IL-2 (rIL-2), recombinant IL-4 (rIL-4)
       or recombinant IL-6 (rIL-6) might restore the response of B cells of
       HIV-infected patients. B cells of 6 HIV-negative hemophilia patients, 4
       HIV-positive patients at CDC stage II, III, 4 HIV-positive patients at
       CDC stage IV, and 6 healthy controls were tested in Staphylococcus
       aureus Cowan I (SAC-I)-stimulated B cell cultures and Pokeweed mitogen
       (PWM)-stimulated allogeneic B and T cell cocultures. B cell
       differentiation was assessed in a reverse hemolytic plaque assay and by
       ELISA determination of IgM, IgG and IL-6 in culture supernatants. In
       vitro application of rIL-6 resulted in suppression of both elevated
       unstimulated and mitogen-stimulated B cell responses in a dose-dependent
       manner which was in part due to feedback inhibition. PWM- and
       SAC-I-stimulated IgG and IgM responses, respectively, could be restored
       after addition of 10 U/ml rIL-2 in HIV-negative patients, but not in
       HIV-positive patients. Addition of rIL-4 to cultures resulted in
       suppression of both unstimulated and mitogen-stimulated IL-6 secretion
       and B cell responses. Severely depressed B cell responses in CDC IV
       patients were not significantly affected by cytokine application. These
       results indicate that defective Ig responses in HIV-negative patients
       may be restored by rIL-2 treatment whereas HIV-induced B cell defects
       are not corrected by supply of T cell help or cytokines promoting B cell
       growth and differentiation.
 DE    Autoantibodies/*BIOSYNTHESIS  B-Lymphocytes/*DRUG EFFECTS  Blood
       Coagulation Factors/*ADVERSE EFFECTS  Cell Differentiation/DRUG EFFECTS
       Cell Division/DRUG EFFECTS  Cells, Cultured
       Hemophilia/COMPLICATIONS/*DRUG THERAPY/IMMUNOLOGY  Human  HIV
       Infections/*DRUG THERAPY/ETIOLOGY/IMMUNOLOGY  Immune Tolerance
       Interleukins/*PHARMACOLOGY  Pokeweed Mitogens/PHARMACOLOGY  Recombinant
       Proteins/PHARMACOLOGY  Staphylococcus aureus/METABOLISM  Stimulation,
       Chemical  JOURNAL ARTICLE

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

