Role of nitric oxide in the promoting effect of HIV type 1 infection and of gp120 envelope glycoprotein on interleukin 4-induced IgE production by normal human mononuclear cells

Increased levels of serum IgE have been described in HIV-1 infection; howev er, mechanisms implicated in this immunoglobulin production remain unknown. In this study, we demonstrate that in vitro infection of human peripheral blood mononuclear cells (PBMCs) by HIV-1 monocytotropic (Ba-L) or lymphocyt otropic (LAI) strains promotes IL-4-induced IgE production, indicating that the HIV-1 infectious process may participate in the IgE production observe d in vivo. The effect of membrane glycoproteins (gp160, gp120, and gp41) wa s also evaluated. It was found that gp120 specifically potentiates in a dos e-dependent manner IL-4-induced IgE production and does not affect IL-4-ind uced IgG, IgA, or IgM production. In these experiments, gp160 was also foun d to upregulate IL-4-induced IgE production, whereas gp41 was ineffective. This effect of gp120, gp160, and HIV-1 infection on IgE synthesis was not o bserved in the absence of IL-4. In the presence of IL-4, the inducing effec t of gp120 appeared to be indirect because gp120 did not modify purified B lymphocyte IgE production after IL-4 and anti-CD40 monoclonal antibody stim ulation. As HIV-1 infection is associated with alterations of PBMC redox me tabolism, the role of nitric oxide (NO) in this IgE production by human PBM Cs was evaluated. In the presence of a specific inhibitor of NO synthase pa thways (L-NAME), IgE production induced by IL-4 and gp120 was abolished. Ta ken together, these data indicate that HIV-1 envelope glycoprotein gp120 la nd gp160) specifically enhances IL-4-induced IgE production by normal human PBMCs, probably through the regulation of the nitric oxide pathway.