Cytokine Polymorphisms and Susceptibility to Severe Infectious Diseases

Cytokines are key regulators of the host response to infection, controlling the inflammatory reaction which is an essential component of the defense mechanisms. The major importance of these proteins in the pathogenesis and outcome of infectious diseases has been clearly demonstrated. In humans, there is increasing evidence that the host's cytokine response is genetically determined and that the genetic variability of cytokines underlies the complexity of interindividual differences in the immune response to micro organism invasions. We review the influence of host cytokine gene on the susceptibility to and the severity of parasitic, bacterial and viral infections. Proinflammatory cytokine polymorphisms are discussed in detail because of their importance in the course of severe infections such as meningococcal disease, cerebral malaria and septic shock. Genetic variants of the IL-10 gene, an antiinflammatory cytokine appear to be responsible for an uncontrolled and intense CARS and may have also dramatic consequences as an overwhelming inflammatory response. Our greater understanding of the genetic factors that influence mortality and morbidity of infectious diseases will permit identification of genomic markers which may be required for risk stratification of patients targeted for novel immunomodulatory treatments helping clinicians to select the most appropriate treatment options for their patients.