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

Department of Medicine III and Institute of Medical Microbiology and Hygiene, University of Schleswig Holstein, Campus Lübeck, Lübeck; and Medical Clinic and Department of Immunology and Cell Biology, Research Center Borstel, Borstel, Germany

Correspondence and requests for reprints should be addressed to Klaus Dalhoff, M.D., Medizinische Klinik III, Medizinische Universität zu Lübeck, Ratzeburger Allee 160, 23538 Lübeck, Germany. E-mail: klaus.dalhoff{at}medinf.mu-luebeck.de

Polymorphisms in the tumor necrosis factor and interleukin-10 genes, linked to cytokine inducibility, may influence the inflammatory 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 pneumonia, 5 patients with meningitis, and 3 patients with pneumonia and meningitis) and 50 age-matched control subjects were included. The polymorphisms were determined by the polymerase chain reaction. In patients with pneumococcal disease, the lipopolysaccharide-stimulated tumor necrosis factor and interleukin-10 release from whole blood were measured by ELISA. Sepsis severity was documented according to standard criteria. No significant genotypic differences were seen between patients and control subjects. 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 interval, 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 impaired bacterial clearance.

Key Words: tumor necrosis factor- polymorphism • lymphotoxin- polymorphism • genetic predisposition

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