Cytokine Expression During Syphilis Infection in HIV–1-Infected Individuals

Abstract

Little is known about cytokine responses to syphilis infection in HIV-1-infected individuals. We retrospectively identified patients with HIV-1 and Treponema pallidum coinfection. Plasma samples from before, during, and after coinfection were analyzed for interleukin (IL)-2, IL-4, IL-6, IL-8, IL-10, interferon (IFN)-gamma, and tumor necrosis factor (TNF)-alpha. Thirty-six patients were included. IL-10 levels increased significantly in patients with primary or secondary stage syphilis from a median of 12.8 pg/mL [interquartile range (IQR), 11.0-27.8] before infection to 46.7 pg/mL (IQR, 28.4-78.9) at the time of diagnosis (P = 0.027) and decreased to 13.0 pg/mL (IQR, 6.2-19.4) after treatment of syphilis (P <0.001). TNF-alpha levels showed no significant change from before to during syphilis in patients with primary or secondary stage syphilis (median 3.9 pg/mL (IQR, 3.3-9.6) and 9.0 pg/mL (IQR, 5.4-12.6), respectively (P = 0.31); however, treatment of syphilis was associated with a significant decrease in TNF-alpha to a median of 4.2 pg/mL (IQR, 2.7-6.8) (P <0.001). No significant changes in cytokine levels were observed in coinfected with latent stage syphilis.IL-10 and TNF-alpha levels correlated positively with plasma HIV RNA values at the time of diagnosis (r = 0.38, P = 0.023, and r = 0.64, P <0.001, respectively) and correlated inversely with CD4 T cell counts (-0.35, P = 0.036 and r = -0.34, P = 0.042, respectively). HIV-1 and early stage syphilis coinfection were associated with an increase in IL-10. IL-10 and TNF-alpha both decreased after treatment of syphilis. TNF-alpha and IL-10 correlated with low CD4 T cell counts and high plasma HIV RNA values.