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Infection and Immunity, September 2000, p. 5198-5204, Vol. 68, No. 9
0019-9567/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

Cytokine Responses to Plasmodium falciparum Liver-Stage Antigen 1 Vary in Rainy and Dry Seasons in Highland Kenya

C. C. John,1,* P. O. Sumba,2 J. H. Ouma,3 B. L. Nahlen,4 C. L. King,1 and J. W. Kazura1

Division of Geographic Medicine, Case Western Reserve University School of Medicine and University Hospitals of Cleveland, Cleveland, Ohio1; Kenya Medical Research Institute, Kisian,2 and Division of Vector Borne Diseases, Ministry of Health, Nairobi,3 Kenya; and Division of Parasitic Diseases, National Center for Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia4

Received 19 January 2000/Returned for modification 17 March 2000/Accepted 12 June 2000

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 to Plasmodium falciparum liver-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-gamma ), and tumor necrosis factor alpha (TNF-alpha ) by peripheral blood mononuclear cells (PBMC) from 17 to 73% of individuals in both age groups in both seasons. IL-10 and TNF-alpha 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-gamma and IL-5 responses. Children produced 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-driven IL-10 and TNF-alpha responses requires repeated and sustained exposure to liver-stage P. falciparum. In contrast, IFN-gamma responses increase slowly with age but persist once acquired. CD8+ T cells are the major source of IFN-gamma but may suppress production or secretion of IL-10.

* Corresponding author. Mailing address: Division of Geographic Medicine, Case Western Reserve University School of Medicine, W137, 2109 Adelbert Road, Cleveland, OH 44106-4983. Phone: (216) 844-3645. Fax: (216) 368-4825. E-mail: ccj{at}po.cwru.edu.

Infection and Immunity, September 2000, p. 5198-5204, Vol. 68, No. 9
0019-9567/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.


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