Polymorphic Variability in the Interleukin (IL)-1β Promoter Conditions Susceptibility to Severe Malarial Anemia and Functional Changes in IL-1β Production

• Published in: The Journal of infectious diseases Vol. 198; no. 8; pp. 1219 - 1226
• Main Authors: Ouma, Collins, Davenport, Gregory C., Awandare, Gordon A., Keller, Christopher C., Were, Tom, Otieno, Michael F., Vulule, John M., Martinson, Jeremy, Ong'echa, John M., Ferrell, Robert E., Perkins, Douglas J.
• Format: Journal Article
• Language: English
• Published: Chicago, IL The University of Chicago Press 15.10.2008; University of Chicago Press
• Subjects: Anemia; Biological and medical sciences; Cytokines; Disease susceptibility; Falciparum malaria; Fundamental and applied biological sciences. Psychology; Haplotypes; Hemoglobins; Human protozoal diseases; Infectious diseases; Interleukins; Malaria; Medical sciences; Microbiology; Parasitemia; Parasites; Parasitic diseases; Protozoal diseases; Infection; Protozoal disease; Sensitivity; Microbiology; Malaria; Anemia; Cytokine; Interleukin 1β; Hemopathy; Parasitosis
• ISSN: 0022-1899; 1537-6613
• DOI: 10.1086/592055

Interleukin (IL)-1β is a cytokine released as part of the innate immune response to Plasmodium falciparum. Because the role played by IL-1β polymorphic variability in conditioning the immunopathogenesis of severe malarial anemia (SMA) remains undefined, relationships between IL-1β promoter variants (-31C/T and -511A/G), SMA (hemoglobin [Hb] level <6.0 g/dL), and circulating IL-1β levels were investigated in children with parasitemia (n = 566) from western Kenya. The IL-1β promoter haplotype -31C/-511A (CA) was associated with increased risk ofSMA(Hb level <6.0 g/dL; odds ratio [OR], 1.98[95%confidence interval {CI}, 1.55–2.27]; P < .05) and reduced circulating IL-1β 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-1β production (P < .05). Compared with the non-SMA group, children with SMA had significantly lower IL-1β levels and nonsignificant elevations in both IL-1 receptor antagonist (IL-1Ra) and the ratio of IL-1Ra to IL-1β. The results presented demonstrate that variation in IL-1β promoter conditions susceptibility to SMA and functional changes in circulating IL-1β levels.