A TAENIA-SOLIUM METACESTODE FACTOR NONSPECIFICALLY INHIBITS CYTOKINE PRODUCTION

Studies of the immune response in chronic helminth infections suggest that parasites modulate the host's immune response. Taenia solium meta cestodes, in particular, produce molecules that down-regulate cell-med iated immunity. We have described a small RNA peptide termed metacesto de factor (MF) that depresses the murine immune response to Salmonella typhimurium antigens. MF inhibits mitogen-induced proliferation, humo ral and cellular responses to metacestode antigens, and inflammation s urrounding metacestodes implanted subcutaneously in mice. To assess th e effects of MF on cytokine production we stimulated murine spleen cel ls in vitro with concanavalin A and measured cytokine concentrations i n the culture supernatants by enzyme-linked immunosorbent assay. When cultured with MF, the cells showed significantly decreased production of interleukin 2 (IL-2), interferon-gamma (IFN-gamma), and IL-4 as com pared with mitogen alone. Exogenous rIL-2 and rIL-4 largely restored t he proliferative response (85% and 71% of control cells, respectively) . MF also decreased production of tumor necrosis factor-alpha (TNF-alp ha) by macrophages stimulated with lipopolysaccharide and IFN-gamma. T he TNF-alpha concentration was inversely correlated with the MF concen tration. Experiments using spleen cells from mice treated with MF also showed a significant reduction in IL-4 concentration. These results s uggest that MF inhibits cytokine production without regard to cell typ e or cytokine. This may explain the function of this molecule as an in hibitor of the host inflammatory and immune responses.