The interleukin-6 -174 promoter polymorphism is associated with extrapulmonary bacterial dissemination in Streptococcus pneumoniae infection.

Interleukin-6 (IL-6) is required for the clearance of bacteria in pneumococcal pneumonia. The abundance of endogenous IL-6 production on infectious stimuli is associated with genotypic differences in the -174 promoter region of IL-6 (-174 G-->C), showing increased IL-6 levels in patients carrying the GG genotype. One hundred patients with culturally proven pneumococcal disease were analyzed for distribution of the G-/C-alleles in the IL-6 -174 promoter region in comparison to 50 age-matched controls. Extrapulmonary pneumococcal dissemination, including septic metastasis, endocardial and meningeal infection, was used as parameter for impaired clearance of the bacteria. No significant differences in the allele distribution were observed between patients and controls. Within the patient group, the interleukin-6 GG homozygous carriers were less likely to develop extrapulmonary pneumococcal infection (10.3% versus 30.9%; OR 0.26, 95% CI 0.07-0.94, p=0.04). The IL-6 GG genotype, encoding for enhanced IL-6 secretion on bacterial stimuli, reduces the risk of bacterial spread to extrapulmonary sites in pneumococcal infection, possibly due to a more effective clearance of the pathogen from the blood and the respiratory tract.

Pneumococcal septic shock is associated with the interleukin-10-1082 gene promoter polymorphism.

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-alpha-308 promoter, and the lymphotoxin-alpha 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.