Analysis of the Polymorphisms of Th1 and Th17 Cytokines in Mediterranean Spotted Fever

Background: We have recently reported that the susceptibility for Mediterranean spotted fever (MSF) caused by Rickettsia conorii, is influenced by the Th2 and Th1 cytokine genetic polymorphism profiles. Less it is known on the effect of gene polymorphisms of cytokine produced by the Th17. Methods: 70 Sicilian patients affected by MSF and 239 control subjects matched for age, gender, and geographic origin were typed for functionally relevant single nucleotide polymorphisms (SNPs) of IFN-γ (+874 T/A), IL-18 (-137 G/C and -607A/C ) and IL-17 (7488T/C) according to our laboratory procedures. Results: No significant differences in IL-18 -137 G/C, -607A/C and in IFN-γ +874 T /A genotype frequencies were observed. On the contrary a statistically significant (p value= 0.0126) increase of the IL-17 TT genotype frequency of in MSF was observed. Conclusions: Cytokines play a crucial role in modulation of the host defense and genetically determined differences in cytokine production seem to influence the extent and severity of a large number of infectious diseases. 7488T/C SNP impinge on IL-17 signaling and might play a crucial role in neutrophil recruitment, induction of IFN-γ and IL-12 production in macrophages and in the induction of T regulatory cells. Our results suggest that a genetically determined increase of IL-17 dependent activation pathways might interfere with R. Conorii infection control.