Cytokine polymorphisms

<p>Cytokine polymorphisms have a synergistic effect on severity of the acute sickness response to infection.

Vollmer-Conna U, Piraino BF, Cameron B, Davenport T, Hickie I, Wakefield D, Lloyd AR; Dubbo Infection Outcomes Study Group.

Collaborators (8)

School of Psychiatry and 2Centre for Infection and Inflammation Research, School of Medical Sciences, University of New South Wales, Sydney, Australia.

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.&nbsp;

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.&nbsp;

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.&nbsp;

CONCLUSIONS: These findings suggest that genetically determined variations in the intensity of the inflammatory response underpin the severity of the acute sickness response and predict the recovery time across varied infections.</p>