Salivary Th1/Th2 Cytokine Alterations in Naive HIV-2 and HIV-1 Infection

Objectives: To characterize the oral host response in HIV infection, focusing Th1 (IFN-γ, IL-12, IL-2, IL-8, TNF-α) and Th2 (IL-10, IL-13, IL-1β, IL-4, IL-5) cytokine expression comparing naive HIV-2 and HIV-1 infections.
Methods: This was a cross-sectional study involving 3 study groups: HIV-2+ and HIV-1+ ART-naïve subjects and a control group of seronegative subjects. Oral examination was performed and whole stimulated saliva samples were collected. and analysed for the expression of a panel of 10 Th1/Th2 cytokines using an electrochemiluminescence sandwich assay (MesoScaleDiscovery^TM). Correlations between dependent and potential co-variates were analyzed using Pearson, Spearman correlations or Phi coefficient as appropriate. Mean values comparison between groups (HIV-1+, HIV-2+ and HIV negative groups were performed using one-way ANOVA. Multivariate analysis was performed to identify the variables associated with cytokine expression.
Results: A total of 60 subjects were enrolled (20 HIV-1+, 20 HIV-2+ and 20 HIV negative). Increase in IL-10 and IL-5 levels was observed in HIV positive subjects comparing to HIV-negative subjects, which was only significant for HIV-1+ (p<0.05). Th2-associated cytokine expression (IL-10, IL-5 and IL-13) was consistently observed to be intermediate in HIV-2 group (HIV-p<0.05). Pro-inflammatory cytokine (IL-8 and IL-1β) levels were positively correlated to the prevalence and severity of periodontal disease in all study groups (p<0.05).
Conclusions: HIV infection, in particular HIV-1 was associated to a clear increase in the expression of salivary Th2 (IL-10, IL-13 and IL-5) cytokines while HIV-2+ subjects displayed a Th2/Th1 balance closer to HIV-negative group. Our results suggest a role for CD8+ cells in determining the nature of local oral responses that should be further studied, as it may contribute to explain the milder clinical behavior of HIV-2 infection.