Genetic Variation at the IL10 Gene Locus Is Associated with Severity of Respiratory Syncytial Virus Bronchiolitis

The intense airway inflammatory response associated with respiratory syncytial virus (RSV) infection may be an important determinant in the severity of the disease. Interleukin (IL)–10 is a key regulatory cytokine known to be secreted during this infection. We investigated the role that IL-10 plays in RSV disease by studying the effects that variation in the IL10 gene has on the outcome of the disease. Eight single nucleotide polymorphisms (SNPs) spanning the IL10 gene were selected, and haplotypes were constructed. SNPs that efficiently tagged these haplotypes were then typed in 580 infants with severe RSV bronchiolitis and in 580 control subjects. None of the SNPs or haplotypes was associated with RSV bronchiolitis. In a subgroup analysis, 2 SNPs (IL10 1117 and IL10 3585) were associated (odds ratio, 1.7; ) with the need for mechanical ventilation.Pp.004 These data are consistent with the theory that IL10 plays a role in the severity of RSV infection in infants. Bronchiolitis caused by respiratory syncytial virus (RSV) is the most common reason that infants in the devel-oped world are admitted to the hospital [1], and it is an important contributor to morbidity and mortality in infants worldwide. By the end of their second winter, nearly all infants will have been infected with RSV [2]. The majority of infected infants will have coryzal symp-toms with or without a cough. A small proportion (1%– 2%) develop severe lower respiratory tract disease that necessitates supportive care in the hospital. The host response to RSV appears to be an important determi-nant of the severity of the disease. It has been suggested on the basis of mouse models of RSV infection that a Th2-weighted immune response favors the development of severe bronchiolitis [3]. Some studies of the levels of Th1 and Th2 cytokines in nasa