PRODUCTION OF INTERLEUKIN-10 DURING MALARIA CAUSED BY LETHAL AND NONLETHAL VARIANTS OF PLASMODIUM-YOELII YOELII

We investigated the induction of T-helper cell subsets during the cour se of lethal or nonlethal blood-stage Plasmodium yoelii 17X infection in C57BL/6 mice, which are relatively susceptible to these intraerythr ocytic parasites. C57BL/6 mice infected with the nonlethal variant (Py NL) showed a moderate level of parasitemia and resolution of primary a cute infection by week 4. Mice infected with the lethal variant (PyL) developed fulminating parasitemia and ultimately died. T-helper subset function was assessed during infection by determining the kinetics of in vitro production of the Th1-derived cytokine interferon-gamma (IFN -gamma) and the Th2-derived cytokine interleukin 10 (IL-10) by means o f bioassay and enzyme-linked immunosorbent assay (ELISA), respectively . Spleen cells obtained from mice infected with PyL within the 1st wee k of infection produced high levels of IL-10 and IFN-gamma in response to malaria antigen. IL-10 also appeared in sera from PyL-infected mic e at the same time at which the in vitro IL-10 response peaked. In con trast, spleen cells from mice infected with PyNL failed to produce IL- 10 during the course of infection. CD4(+) T-lymphocytes from mice infe cted with the lethal variant were a major source of IL-10, although no n T-cells were also involved in the production of IL-10 during this ma laria infection. In addition, the initial burst of IL-10 in response t o malaria antigens was seen concomitantly with the production of IFN-g amma within the 1st week of infection. These results indicate that bot h Th1 and Th2 subsets of T-helper lymphocytes are activated during inf ection with the lethal variant of P. yoelii and support the contention of other investigators that a strong Th2 response early in infection is associated with the lethal outcome of malaria.