Objectives Recent studies suggested that upregulation of anti-inflammatory immune response during early syphilis may be associated with persistence of Treponema pallidum infection despite adequate treatment, resulting in a serofast state. The objective of this study was to determine whether enhanced interleukin (IL)-10-related response during early T. pallidum infection increased the risk of serofast syphilis.

Methods Two IL10 gene promoter polymorphisms affecting IL-10 production (−1082A>G [rs1800896], −592C>A [rs1800872]) and serum levels of IL-10 were measured in 80 patients with early syphilis before and 6 months after penicillin treatment and in 24 healthy volunteers (control group).

Results After 6 months, patients were stratified based on serological response into two groups: (1) serofast state (n = 28) and (2) serologically cured (n = 52). Pretreatment and post-treatment serum IL-10 levels were significantly higher in patients who remained serofast compared with those who had a serological cure (p<0.001). The GG genotype of the −1082A>G (rs1800896) polymorphism and the CC genotype of the −592C>A (rs1800872) polymorphism were significantly correlated with higher serum IL-10 levels. Moreover, the OR for remaining serofast for carriers of these genotypes was 16.2 (95% CI: 4.1 to 65.0, p<0.0001) and 2.9 (95% CI: 1.4 to 5.9, p=0.002), respectively.

Conclusions We showed that a pronounced anti-inflammatory immune response may be an important predictor for the serofast state. Additionally, host-related factors such as polymorphisms of immune regulatory genes may influence the risk of remaining serofast after syphilis therapy.