Cytokine Polymorphisms in Men with Chronic Prostatitis/Chronic Pelvic Pain Syndrome: Association with Diagnosis and Treatment Response

Abstract

The chronic pelvic pain syndrome is a common disorder of unknown etiology. Elevated cytokines in prostate fluid and semen are frequent findings. We studied genetic polymorphisms that can alter cytokine gene expression in men with the chronic pelvic pain syndrome. Genomic DNA was extracted from blood from 36 men with the chronic pelvic pain syndrome. Reversed sequence specific oligonucleotide probing was used to genotype the polymorphisms for cytokine promoter sites, namely tumor necrosis factor (TNF)-alpha 308, transforming growth factor (TGF)-beta 25, TGF-beta 10, interleukin (IL)-10 1082 and IL-6 174. Genotype frequencies were compared with 252 controls as well as among groups of patients with the chronic pelvic pain syndrome according to diagnostic category and treatment response. There were no differences in men with the chronic pelvic pain syndrome and control patients in the frequency of TNF-alpha, TGF-beta or IL-6 alleles, although those with the chronic pelvic pain syndrome were more likely to express the genotype associated with low IL-10 production (30.6% versus 12.1%, p = 0.007). When comparing National Institutes of Health diagnoses, category IIIa patients were more likely to have the low TNF-alpha genotype (categories II, IIIa and IIIb 33%, 100% and 18%, respectively, p = 0.04). All 11 of the 28 patients treated with the anti-inflammatory quercetin in whom treatment failed had the low TNF-alpha genotype versus 29.4% of those in whom treatment succeeded (p = 0.0003). Similarly men with quercetin treatment failure were much less likely to have the low IL-10 genotype than those with treatment success (9.1% versus 47.1%, p = 0.04). Patients with the chronic pelvic pain syndrome are more likely to have a low IL-10 producing genotype, suggesting autoimmunity as a potential etiology. Anti-inflammatory phytotherapy failure was associated with low TNF-alpha and high IL-10 phenotypes, which may help define a subset of patients with the chronic pelvic pain syndrome without an inflammatory etiology.