Journal
CLINICAL INFECTIOUS DISEASES
Volume 47, Issue 11, Pages 1418-1425Publisher
OXFORD UNIV PRESS INC
DOI: 10.1086/592967
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Funding
- National Health and Medical Research Council of Australia [157092, 157062]
- Meat and Livestock Australia
- Cooperative Research Agreement with the US Centers for Disease Control and Prevention [U50/CCU019851-01]
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Background. Functional polymorphisms in immune response genes are increasingly recognized as important contributors to the marked individual differences in susceptibility to and outcomes of infectious disease. The acute sickness response is a stereotypical set of illness manifestations mediated by the proinflammatory cytokines induced by many different pathogens. The genetic determinants of severity of the acute sickness response have not previously been explored. Methods. We examined the impact of functional polymorphisms in cytokine genes with critical roles in the early immune response (tumor necrosis factor-alpha, interleukin-6, interleukin-10, and interferon-gamma) on the severity and duration of illness following acute infection with Epstein-Barr virus, Coxiella burnetii (the causative agent of Q fever), or Ross River virus. Results. We found that the interferon-gamma + 874T/A and the interleukin-10 - 592C/A polymorphisms significantly affected illness severity, cytokine protein levels, and the duration of illness. These cytokine genotypes acted in synergy to potentiate their influence on disease outcomes. Conclusions. These findings suggest that genetically determined variations in the intensity of the inflammatory
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