Cytokine Responses toPlasmodium falciparumLiver-Stage Antigen 1 Vary in Rainy and Dry Seasons in Highland Kenya

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Abstract
Seasonal epidemics of malaria occur in highland areas of western Kenya where transmission intensity varies according to rainfall. This study describes the seasonal changes in cytokine responses toPlasmodium falciparumliver-stage antigen 1 (LSA-1) by children (≤17 years old) and adults (≥18 years old) living in such a highland area. Fourteen- to 24-mer peptides corresponding to the N- and C-terminal nonrepeat regions of LSA-1 stimulated production of interleukin-5 (IL-5), interleukin-10 (IL-10), gamma interferon (IFN-γ), and tumor necrosis factor alpha (TNF-α) by peripheral blood mononuclear cells (PBMC) from 17 to 73% of individuals in both age groups in both seasons. IL-10 and TNF-α responses were more frequent during the high-transmission, rainy season than during the low-transmission, dry season (73 and 67% versus 17 and 25% response rates, respectively). In contrast, there was no seasonal change in the proportion of LSA-1-driven IFN-γ and IL-5 responses. Children produced less IFN-γ than adults, but IL-5, IL-10, and TNF-α levels were similar for both age groups. Depletion of CD8+cells from PBMC decreased IFN-γ 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-driven IL-10 and TNF-α responses requires repeated and sustained exposure to liver-stageP. falciparum. In contrast, IFN-γ responses increase slowly with age but persist once acquired. CD8+T cells are the major source of IFN-γ but may suppress production or secretion of IL-10.