Results from the CAPRISA 002 Acute Infection study, investigating the influence of Interleukin-10 promoter polymorphisms on susceptibility and primary HIV-1 pathogenesis was published in the Journal of Infectious Diseases earlier this year.

 

The Interleukin-10 (IL-10) proximal promoter region consists of 2 known bi-allelic polymorphisms, which are related to levels of IL-10 production. Polymorphisms resulting in decreased production have been shown to increase likelihood of HIV-1 acquisition and accelerate CD4 decline. This has led to the suggestion that IL-10 may protect against disease progression. However, more recent animal models with lymphocytic choriomeningitis virus have suggested that removal of IL-10 enhanced T cell immune responses, development of antiviral memory and viral clearance.

 

In this study, the CAPRISA Acute Infection team aimed to develop better insight into the complex role of IL-10 in HIV-1 infection and pathogenesis. Specifically, they investigated if genetic polymorphisms in the proximal region of the IL-10 gene promoter contributed to HIV-1 susceptibility and to primary HIV-1 pathogenesis in an African cohort at high risk for infection.

 

The findings demonstrate that carriers of the - 592AA genotype were more likely to become HIV-1 infected which is in keeping with a study in a North American cohort. In general, the study found that higher-producing IL-10 polymorphisms were associated with high viral load during the acute infection phase. However, as infection progressed to chronic phase, differences in viral load between the genotype groups either disappeared or reversed. Overall, the data from this study proposes a model for the role of IL- 10 in HIV-1 susceptibility and disease progression, whereby high levels of IL-10 protect against HIV-1 infection, possibly by reducing immune activation and counteracting inflammatory processes that increase the pool of susceptible cells, and low levels of IL-10 may have the opposite effects. During acute HIV-1 infection, high IL-10 levels may promote viral replication by dampening innate and adaptive effector immune responses in a manner similar to that described for the LCMV model.

 

For a detailed understanding please refer to the Journal of Infectious Disease, 1 August 2009.