Polymorphic variability in the interleukin (IL)-1beta promoter conditions susceptibility to severe malarial anemia and functional changes in IL-1beta production

Interleukin (IL)-1 is a cytokine released as part of the innate immune response to Plasmodium falciparum. Because the role played by IL-1 polymorphic variability in conditioning the immunopathogenesis of severe malarial anemia (SMA) remains undefined, relationships between IL-1promoter variants (31C/T and511A/ G), SMA (hemoglobin [Hb] level<6.0 g/dL), and circulating IL-1 levels were investigated in children with par-asitemia (n 566) from western Kenya. The IL-1 promoter haplotype31C/511A (CA) was associated with increased riskofSMA(Hb level<6.0g/dL;odds ratio [OR], 1.98 [95%confidence interval {CI}, 1.55–2.27];P<.05) and reduced circulating IL-1 levels (P<.05). The TA (31T/511A) haplotype was nonsignificantly associated with protection against SMA (OR, 0.52 [95 % CI, 0.18–1.16]; P .11) and elevated IL-1 production (P<.05). Compared with the non-SMA group, children with SMA had significantly lower IL-1 levels and nonsignificant elevations in both IL-1 receptor antagonist (IL-1Ra) and the ratio of IL-1Ra to IL-1. The results presented dem-onstrate that variation in IL-1 promoter conditions susceptibility to SMA and functional changes in circulating IL-1 levels. Malaria is a leading global cause of morbidity and mor-tality of infectious disease origin [1]. Approximately 200 million clinical cases of malaria occur among pop