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Elevated Cerebrospinal Fluid Interleukin-17A and Interferon-γ Levels in Early Asymptomatic Neurosyphilis

Pastuszczak, Maciej MD*; Jakiela, Bogdan MD, PhD; Wielowieyska-Szybinska, Dorota MD, PhD*; Jaworek, Andrzej K. MD, PhD*; Zeman, Jacek MD*; Wojas-Pelc, Anna MD, PhD*

doi: 10.1097/OLQ.0000000000000024
Original Study

Background The mechanisms underlying the process of Treponema pallidum clearance from the central nervous system have not yet been established. Considering that neurosyphilis is associated with mild cerebrospinal fluid (CSF) pleocytosis with a lymphocytic predominance, it has been suggested that cells involved in the adaptive immune response may play a role in this process. In the current study, we assessed the cytokine production profile of T-helper cells in the serum and CSF of patients with early syphilis, with and without CSF abnormalities.

Methods Cerebrospinal fluid and blood samples were collected from 33 patients with secondary and early latent syphilis. Five patients (15%) had a reactive CSF Venereal Disease Research Laboratory test without any accompanying neurological symptoms. According to the Centers of Disease Control and Prevention classification, they were diagnosed with asymptomatic neurosyphilis. Serum and CSF levels of interferon-γ (IFN-γ; Th1-type cytokine), interleukin-4 (IL-4; Th2-type cytokine), and interleukin-17A (IL-17A; Th17-type cytokine) were determined by enzyme-linked immunosorbent assay.

Results Patients with asymptomatic neurosyphilis had significantly higher levels of IL-17A (8-fold) and IFN-γ (7.8-fold) in the CSF compared with patients in the no-neurosyphilis group. Six individuals had CSF pleocytosis but a negative CSF Venereal Disease Research Laboratory test result (presumptive neurosyphilis group). In this group, CSF IFN-γ and CSF IL-17A levels were also significantly elevated when compared with no-neurosyphilis group. There was no correlation between serum and CSF concentrations of IL-17A. However, CSF pleocytosis correlated positively with both CSF IL-17A (r = 0.4, P = 0.01) and IFN-γ (r = 0.42, P = 0.01).

Conclusions Increased CSF levels of IFN-γ and IL-17A in syphilitic patients with CSF abnormalities suggest that cells of adaptive immunity (probably T-helper cells producing IFN-γ and IL-17) may contribute to the inflammatory response associated with neurosyphilis. In addition, the lack of correlation between serum and CSF IL-17A levels suggests intrathecal production of this cytokine. Further studies are needed to establish the exact nature of the immune response accompanying neurosyphilis and its clinical significance.

We found that patients with asymptomatic neurosyphilis have elevated levels of interleukin-17A and interferon-γ in the cerebrospinal fluid. This suggests that interferon-γ/interleukin-17A–producing cells may play a role in the immune response in neurosyphilis.

From the Departments of *Dermatology and †Medicine, Jagiellonian University School of Medicine, Cracow, Poland

Conflict of interest: None declared.

Correspondence: Maciej Pastuszczak, MD, Department of Dermatology, School of Medicine, 31-066 Cracow, Poland, Skawinska 8 Street. E-mail:

Received for publication April 13, 2013, and accepted June 25, 2013.

© Copyright 2013 American Sexually Transmitted Diseases Association