title: In vitro cytokine treatment of B cell defects in HIV-infected hemophilia patients.
abstract: 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.
mesh_terms: D001323:Autoantibodies / Q000096:biosynthesis*; D001402:B-Lymphocytes / Q000187:drug effects*; D001779:Blood Coagulation Factors / Q000009:adverse effects*; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D015658:HIV Infections / Q000188:drug therapy* / Q000209:etiology / Q000276:immunology; D006467:Hemophilia A / Q000150:complications / Q000188:drug therapy* / Q000276:immunology; D006801:Humans; D007108:Immune Tolerance; D007378:Interleukins / Q000494:pharmacology*; D011043:Pokeweed Mitogens / Q000494:pharmacology; D011994:Recombinant Proteins / Q000494:pharmacology; D013211:Staphylococcus aureus / Q000378:metabolism; D013268:Stimulation, Chemical
chemical_list: D001323:Autoantibodies; D001779:Blood Coagulation Factors; D007378:Interleukins; D011043:Pokeweed Mitogens; D011994:Recombinant Proteins