The acute phase of
Mediterranean spotted fever (MSF) is characterized by dramatic changes in
cytokine production patterns, clearly indicating their role in the
immunomodulation of the response against the microorganism, and the differences in
cytokine production seem to influence the extent and severity of the disease. In this study, the single nucleotide polymorphisms (SNPs) of
tumor necrosis factor alpha (
TNF-alpha) -308G/A (rs1800629) and
interleukin-10 (IL-10) -1087G/A (rs1800896), -824C/T (rs1800871), and -597C/A (rs1800872) and the
gamma interferon (IFN-gamma) T/A SNP at position +874 (rs2430561) were typed in 80 Sicilian patients affected by MSF and in 288 control subjects matched for age, gender, and geographic origin. No significant differences in
TNF-alpha -308G/A genotype frequencies were observed. The +874TT genotype, associated with an increased production of IFN-gamma, was found to be significantly less frequent in MSF patients than in the control group (odds ratio [OR], 0.18; 95% confidence interval [95% CI], 0.06 to 0.51; P corrected for the number of genotypes [Pc], 0.0021). In addition, when evaluating the IFN-gamma and
IL-10 genotype interaction, a significant increase of +874AA/-597CA (OR, 5.31; 95% CI, 2.37 to 11.88; P(c), 0.0027) combined genotypes was observed. In conclusion, our data strongly suggest that finely genetically tuned
cytokine production may play a crucial role in the regulation of the immune response against rickettsial
infection, therefore influencing the disease outcomes, ranging from nonapparent or subclinical condition to overt or fatal disease.