Cytokine regulation of antigen-driven immunoglobulin production in filarial parasite infections in humans

Abstract

To define the immunoregulatory mechanisms underlying serum IgE levels found in patients with filariasis, we studied polyclonal IgE production by peripheral blood mononuclear cells (PBMC) from 15 patients with filarial infections, with a focus on the role of interleukin-4 (IL-4) and interferon-gamma (IFN-γ) in the generation and regulation of the response. Spontaneous in vitro IgE production was elevated in 10 of the 15 patients (836-6,464 pg/ml; normals, < 500 pg/ml). Addition of filarial parasite antigen to PBMC cultures significantly stimulated polyclonal IgE production in an antigen dose-dependent manner in 10 of 12 patients tested (P < 0.001). The essential role of IL-4 in the generation of this response was demonstrated when simultaneous addition of anti-IL-4 completely inhibited antigen-stimulated IgE production in all 10 patients studied. An inhibitory role of endogenously produced IFN-γ was also indicated when the addition of anti-IFN-γ to the cultures significantly augmented filarial antigen-stimulated IgE production by 33-1,238% in these same patients. Addition of 10-1,000 U/ml of recombinant human IFN-γ to PBMC completely inhibited parasite antigen-induced IgE production. This study demonstrates that filarial antigen-stimulated IgE production in patients with filariasis is mediated by IL-4 and down regulated by IFN-γ and suggests that the amount of IgE produced depends on the relative quantity of IL-4 and IFN-γ generated by parasite-specific T cells.