Cytokine responses to Plasmodium falciparum liver-stage antigen 1 vary in rainy and dry seasons in highland Kenya

Seasonal epidemics of malaria occur in highland areas of western Kenya wher e transmission intensity varies according to rainfall. This study describes the seasonal changes in cytokine responses to Plasmodium falciparum liver- stage antigen 1 (LSA-1) by children (less than or equal to 17 years old) an d adults (greater than or equal to 18 years old) living in such a highland area. Fourteen- to 24-mer peptides corresponding to the N- and C-terminal n onrepeat regions of LSA-1 stimulated production of interleukin-5 (IL-5), in terleukin-10 (IL-10), gamma interferon (IFN-gamma), and tumor necrosis fact or alpha (TNF-alpha) by peripheral blood mononuclear cells (PBMC) from 17 t o 73% of individuals in both age groups in both seasons. IL-10 and TNF-alph a responses were more frequent during the high-transmission, rainy season t han during the low-transmission, dry season (73 and 67% versus 17 and 25% r esponse rates, respectively). In contrast, there was no seasonal change in the proportion of LSA-1-driven IFN-gamma and IL-5 responses. Children produ ced less IFN-gamma than adults, but IL-5, IL-10, and TNF-alpha levels were similar for both age groups. Depletion of CD8(+) cells from PBMC decreased IFN-gamma but increased IL-10 production. Individuals with LSA-1-stimulated IL-10 responses in the dry season were less likely to become reinfected in the subsequent rainy season than those without IL-10 responses (25% versus 49%; P = 0.083). These data support the notion that maintenance of LSA-1-d riven IL-10 and TNF-alpha responses requires repeated and sustained exposur e to liver-stage P. falciparum. In contrast, IFN-gamma responses increase s lowly with age but persist once acquired. CD8(+) T cells are the major sour ce of IFN-gamma but may suppress production or secretion of IL-10.