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Blood, Vol. 92 No. 10 (November 15), 1998:
pp. 3721-3729
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
Fredrik Müller,
Pål Aukrust,
Ingvild Nordøy, and
Stig S. Frøland
From the 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.
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.
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