Increased Interleukin-17 in Peripheral Blood and Cerebrospinal Fluid of Neurosyphilis Patients

Abstract

Background Treponema pallidum infection evokes vigorous immune responses, resulting in tissue damage. Several studies have demonstrated that IL-17 may be involved in the pathogenesis of syphilis. However, the role of Th17 response in neurosyphilis remains unclear.Methodology/Principal FindingsIn this study, Th17 in peripheral blood from 103 neurosyphilis patients, 69 syphilis patients without neurological involvement, and 70 healthy donors were analyzed by flow cytometry. The level of IL-17 in cerebrospinal fluid (CSF) was quantified by ELISA. One-year follow up for 44 neurosyphilis patients was further monitored to investigate the role of Th17/IL-17 in neurosyphilis. We found that the frequency of Th17 cells was significantly increased in peripheral blood of patients with neurosyphilis, in comparison to healthy donors. IL-17 in CSF were detected from 55.3% neurosyphilis patients (in average of 2.29 (0–59.83) pg/ml), especially in those with symptomatic neurosyphilis (61.9%). CSF IL-17 was predominantly derived from Th17 cells in neurosyphilis patients. Levels of IL-17 in CSF of neurosyphilis patients were positively associated with total CSF protein levels and CSF VDRL (Venereal Disease Research Laboratory) titers. Notably, neurosyphilis patients with undetectable CSF IL-17 were more likely to confer to CSF VDRL negative after treatment.ConclusionsThese findings indicate that Th17 response may be involved in central nervous system damage and associated with clinical symptoms in neurosyphilis patients. Th17/IL-17 may be used as an alternative surrogate marker for assessing the efficacy of clinical treatment of neurosyphilis patients.

Cytokine Profiles in Aqueous Humor and Plasma of HIV-infected Individuals with Ocular Syphilis or Cytomegalovirus Retinitis

“…29,30 In sum, our results support previous findings indicating elevated levels of AqH IP-10 and MCP-1 in individuals with CMVr, 11 and we corroborated the notion of elevated concentrations of MCP-1 and IL-8 previously reported in AqH of individuals with uveitis, 31 as well as the intraocular production of IL-8 by the ciliary processes. 32 In contrast with a study reporting increased concentrations of IL-17 in peripheral blood and cerebrospinal fluid of individuals with neurosyphhilis, 33 we found undetectable levels of this cytokine in plasma.…”

Robust pro-inflammatory immune response is associated with serological cure in patients with syphilis: an observational study

“…IFN-γ-activated macrophages seems to be the most important component of the immune system involved in the eradication of T. pallidum. 5 Moreover, it has been shown that robust pro-inflammatory response at early stages of infection may decrease the risk of progression to later stages of syphilis 6. Hence, the question arose whether serofast state could be associated with a lower magnitude of innate immune response.…”

“…T cells participate in the eradication of treponemas primarily through the production of cytokines such as interferon (IFN)-γ, therefore activating macrophages, which subsequently kill opsonised spirochetes 4 5. It has been shown recently that suppression of pro-inflammatory (IFN-γ) and concomitant activation of regulatory immune responses (interleukin (IL)-10) may facilitate the progression of syphilis towards later stages of the disease 6 7. Hence, the robust pro-inflammatory immune response seems to be crucial to get control over T. pallidum during early infection.…”

Neurosyphilis

“…One study described the proportion of individuals with CSF abnormalities in asymptomatic (n ¼ 40) and symptomatic neurosyphilis (n ¼ 63); data are shown in ►Table 1. 84 The proportion of patients with CSF abnormalities is dependent upon the criteria used to define neurosyphilis. It is important to keep in mind that individuals with HIV with high CD4 þ T cell counts or who are not on ARV treatment or who have detectable plasma HIV RNA may have CSF pleocytosis related to HIV alone.…”