Pneumococcal Septic Shock Is Associated with the Interleukin-10–1082 Gene Promoter Polymorphism

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Abstract
Polymorphisms in the tumor necrosis factor and interleukin-10 genes, linked to cytokine inducibility, may influence the inflamma- tory response to infection. We studied the biallelic interleukin-10- 1082 promoter, the tumor necrosis factor--308 promoter, and the lymphotoxin- polymorphisms with regard to the development of septic shock in pneumococcal infection. Sixty-nine patients with pneumococcal disease (61 patients with community-acquired pneu- monia, 5 patients with meningitis, and 3 patients with pneumonia and meningitis) and 50 age-matched control subjects were in- cluded. The polymorphisms were determined by the polymerase chain reaction. In patients with pneumococcal disease, the lipopoly- saccharide-stimulated tumor necrosis factor and interleukin-10 re- lease from whole blood were measured by ELISA. Sepsis severity was documented according to standard criteria. No significant ge- notypic differences were seen between patients and control sub- jects. Thirteen of 69 patients with pneumococcal disease developed septic shock. Interleukin-10 allele G homozygous patients had the highest risk for septic shock (odds ratio of 6.1; 95% confidence inter- val, 1.4-27.2; corrected p 0.024). The stimulated interleukin-10 release was highest in interleukin-10 G homozygous patients (p 0.04). In conclusion, interleukin-10 polymorphism, associated with high interleukin-10 inducibility, might influence the outcome of pneumococcal infection via induced immunosuppression and im- paired bacterial clearance.