The Th1-th2 profile in immune responses to Human papillomavirus (HPV) in vitro in men from the city of São Paulo, Brazil

Abstract

Introduction: The cell-mediated immune response plays an important role in the control of HPV-induced cancers. Cytokines play an important function in host defense against HPV infection by modulating viral infection and polarizing the immune response towards Th1 or Th2 cells. Objective: To evaluate the specific immune response to HPV in vitro in men with and without lesions caused by HPV. Methods: We recruited 31 patients and 11 volunteers and divided them into the following four groups: 12 patients in Group A (HIV+/HPV+); 9 patients in Group B (HIV-/HPV+); 10 patients in Group C (HIV+/ HPV-); and 11 healthy subjects in Group D (HIV-/HPV-). PBMCs culture assays were performed to measure the levels of Th1/Th2/Th17 cytokines (IFN-γ, IL-2, TNF-α, IL-4, IL-10 and IL-17) in cells from patients stimulated with a quadrivalent HPV vaccine (HPV 6, 11, 16 and 18) and the E7 protein of HPV- 16. Results: The coinfected group A (HIV+/HPV+) showed higher levels of cytokines, especially Th2 cytokines, compared with the other study groups. The coinfected group had significantly higher levels of IL-6 and IL-10, which are Th2 cytokines, compared to the control group (HIV-/HPV-) (p<0.0001 and p<0.0001, respectively). Conclusion: This study reports a high production of cytokines in the coinfected group, suggesting strong immunomodulatory effects by HIV/HPV coinfection. However, further studies should be conducted to confirm these data. Because this group had high levels of Th2 cytokines, especially IL-6 and IL-10, these data suggest that these two cytokines may serve as biomarkers for viral persistence because HIV seropositive patients have a higher HPV persistence and may allow for the progression to more serious injuries to be monitored.