Interleukin-12 (IL-12) is an important regulatory cytokine in infection and immunity. Administration of IL-12 may reduce complications of severe malaria in rodents. Polymorphisms in IL12B, the gene encoding the IL-12 p40 subunit, influence the secretion of IL-12 and susceptibility to Type 1 diabetes. We therefore investigated whether IL12B polymorphisms may affect the outcome of severe malaria. Homozygosity for a polymorphism in the IL12B promoter was associated with increased mortality in Tanzanian children having cerebral malaria but not in Kenyan children with severe malaria. Furthermore, homozygotes for the IL12B promoter polymorphism had decreased production of nitric oxide, which is in part regulated by IL-12 activity. These studies suggest that IL12B polymorphisms, via regulation of IL-12 production, may influence the outcome of malaria infection in at least one African population.
Bibliographical noteFunding Information:
This work was financially supported by the National Health and Medical Research Council of Australia and by a Special Program Grant from the NHMRC and the Juvenile Diabetes Research Foundation; National Institutes of Health RO1 AI41764, NHMRC Scholarship (CSB) and the Wellcome Trust, UK. DJR is a Howard Hughes International Research Scholar. No author has a commercial or other association that might pose a conflict of interest.
- Immune regulation
- Severe malaria
ASJC Scopus subject areas