title: Possible role of interleukin-10 (IL-10) and CD40 ligand expression in the pathogenesis of hypergammaglobulinemia in human immunodeficiency virus infection: modulation of IL-10 and Ig production after intravenous Ig infusion.
abstract: The mechanisms leading to polyclonal hypergammaglobulinemia in patients with human immunodeficiency virus (HIV) infection are not well understood. In light of the important role of interleukin-10 (IL-10) and the interaction between CD40 and CD40 ligand in the normal regulation of B-lymphocyte function and Ig production, we examined these parameters in 24 HIV-infected patients. Both plasma IL-10 levels and the percentage of CD4(+) and CD8(+) lymphocytes expressing CD40 ligand were significantly higher in the patients than in the 10 blood donor controls. Serum IgG correlated positively with circulating IL-10 levels and the percentage of CD4(+) lymphocytes expressing CD40 ligand. Furthermore, a single bolus infusion of intravenous Ig (0.4 g/kg) in 8 HIV-infected patients caused a further increase in IL-10 levels in plasma and an increase in both IL-10 and IgG production in peripheral blood mononuclear cell cultures. In another patient group (Wegener's granulomatosis) receiving a single bolus infusion of intravenous Ig, a similar increase in plasma IL-10 levels was found, suggesting that this may be a general effect of intravenous Ig. In patients with HIV infection, our data suggest that a vicious cycle may be operative where high endogenous Ig levels may enhance IL-10 production that, in turn, leads to higher Ig production.
authors.affiliation: Section of Clinical Immunology and Infectious Diseases, Medical Department A and Research Institute for Internal Medicine, University of Oslo, The National Hospital, Rikshospitalet, Oslo, Norway.
authors.forename: F
authors.initials: F
authors.lastname: Müller
authors.forename: P
authors.initials: P
authors.lastname: Aukrust
authors.forename: I
authors.initials: I
authors.lastname: Nordoy
authors.forename: S S
authors.initials: SS
authors.lastname: Froland
mesh_terms: D000328:Adult; D000917:Antibody Formation; D001402:B-Lymphocytes / Q000276:immunology*; D019013:CD40 Antigens / Q000096:biosynthesis / Q000502:physiology*; D023201:CD40 Ligand; D002478:Cells, Cultured; D005246:Feedback; D005260:Female; D014890:Granulomatosis with Polyangiitis / Q000097:blood / Q000628:therapy; D015658:HIV Infections / Q000097:blood*; D006801:Humans; D006942:Hypergammaglobulinemia / Q000209:etiology / Q000503:physiopathology* / Q000628:therapy; D016756:Immunoglobulins, Intravenous / Q000627:therapeutic use*; D016753:Interleukin-10 / Q000096:biosynthesis / Q000502:physiology*; D008211:Lymphocyte Cooperation; D008297:Male; D008562:Membrane Glycoproteins / Q000096:biosynthesis / Q000502:physiology*; D008875:Middle Aged; D016176:T-Lymphocyte Subsets / Q000276:immunology*
chemical_list: D019013:CD40 Antigens; D016756:Immunoglobulins, Intravenous; D008562:Membrane Glycoproteins; D016753:Interleukin-10; D023201:CD40 Ligand