Interleukin-16 inhibits immunoglobulin e production by B lymphocytes.

Background: The increased production of IgE is a hallmark of atopic disorders. CD4+ T cells regulate the production of Immunoglobulin (Ig) E by B cells. Interleukin (IL) 16, a CD4+ specific cytokine, is highly expressed at sites of allergic inflammation. Our aim was to determine the effect of IL-16 on IgE production in atopic subjects.

Methods: Freshly isolated peripheral blood mononuclear cells (PBMC) from atopic subjects were stimulated with recombinant IL (rIL) 4 and anti-CD40 antibody to promote IgE production in the presence or absence of rIL-16 added at different time intervals prior to stimulation. The levels of IgE in cell culture supernatants collected at day 14 were measured by ELISA. The effect of IL-16 on the expression of the Cepsilon transcript was evaluated by reverse-transcription polymerase chain reaction. To evaluate whether the modulatory effect of IL-16 on IgE production was mediated by interferon-gamma (IFN-gamma), anti-CD40/IL-4-stimulated PBMC were cultured in the presence of rIL-16 and neutralizing concentrations of anti-IFN-gamma antibody.

Results: PBMC stimulated with rIL-4 (400 U/ml) and anti-CD40 monoclonal antibody (0.5 microg/ml) produced significant amounts of IgE (range: 1.3-46.0 ng/ml). The addition of rIL-16 twenty-four hours before stimulation significantly reduced the levels of IgE released by anti-CD40/IL-4-stimulated PBMC (0.5-29.6 ng/ml, p < 0.05). IL-16 reduced the expression of the Cepsilon transcript in stimulated PBMC. IL-16 induced the expression of IFN-gamma mRNA. However, the use of anti-IFN-gamma antibody did not alter the effect of IL-16 on IgE production. Rescue doses of IL-13 did not restore the production of IgE by PBMC treated with IL-16. IL-16 did not alter IgE production in CD14-depleted cell preparations suggesting that the IL-16-mediated effects on IgE production may be related to CD14+ cells.

Conclusions: These data show that IL-16 inhibits IgE production and therefore may play an important regulatory role in atopic disorders.