Differential Expression of Saliva Cytokines in SIV Infected Rhesus Macaque

Objectives: Numerous studies have shown that cytokine levels are elevated in the peripheral blood of HIV-1-infected patients. Few studies have explored features of saliva biomarkers in assessing the oral impact for people living with HIV-1 infection (PLWH). This study compared plasma and salivary cytokine/chemokine levels in rhesus macaques infected with Simian Immunodeficiency Virus (SIV) and healthy control animals. These studies will set the stage to address the oral impact of HIV-1 infection in PLWH on antiretroviral therapy (ART) using an SIV-infected rhesus model on long-term ART.
Methods: Male rhesus macaques were infected with SIVmac251. Plasma and saliva samples were collected when the plasma viral loads were greater than 2.5x10⁴ copies/ml of blood. Controls included uninfected males. The levels of 10 cytokines in saliva and plasma were measured by Mesoscale Discovery assay using a V-Plex cytokine panel-1 NHP kit. To assess whether age and periodontitis in the monkeys could also influence the oral cytokine/chemokine response capabilities, we assessed gene expression levels in gingival tissue in non-SIV-infected animals using microarray analyses.
Results: Saliva levels of GM-CSF, IL-15, IL-17A, IL-5, and TNF-β/LTA were significantly higher in infected animals than controls determined by ANOVA. The saliva levels of IL-1α, IL-16, IL-7, IL-12/IL-23p40, and VEGF were similar in the infected and control animals. Levels of the mRNA for these analytes showed rather minimal differences related to age. Normalized expression of message levels in healthy gingival tissue of normal monkeys showed that IL-1α, TNFβ/LTA, and VEGF were significantly higher with disease, while IL-15 was decreased in periodontitis tissues.
Conclusions: These data provide support for altered salivary and gingival tissue cytokine responses in monkeys infected with SIV. The results suggest that the evaluation of salivary cytokines may serve as a novel target for elucidating the pathophysiology of SIV infection in oral and salivary gland pathobiology.