Proinflammatory, proangiogenic cytokines in saliva and serum in oral leukoplakia

The human oral carcinogenesis milieu typically contains proinflammatory, proangiogenic cytokines . Previously, we have demonstrated that proinflammatory, proangiogenic cytokines could be analyzed in a variety of oral cavity fluids from patients with prenoeplastic epithelial dysplasia(ED), oral squamous cell carcinoma (OSSC) and other lesions. Objectives: In the present study, we analyzed correlations between levels of proangiogenic IL-6, IL-8, and VEGF in saliva and serum in patients with ED (histologically graded as moderate or severe). Methods: Twenty patients with ED were examined, biopsied, and lesions bi-dimensionally measured. Saliva, saline oral rinse and serum were collected and IL-6, 8, and VEGF were analyzed by ELISA. Results: Salivary cytokine levels were 3 to 10 fold higher than serum levels for all three cytokines. A significant correlation was found between VEGF levels in saliva compared to levels in saline oral rinse and serum (p= 0.0004 and 0.0496). For IL-8, there was significant correlation between levels in saliva and saline oral rinse (p=0.0142), but not in serum. In this study, IL-6 levels were much lower and no significant correlation was seen between saliva, saline oral rinse and serum levels. IL-8 and VEGF, but not IL-6, were coordinately upregulated in saliva specimens (p<0.0001). Finally, no correlation was detected between any of the cytokines from the three sources and the size of the index leukoplakia lesions. Conclusions: We conclude that VEGF occurs at the highest levels of the three cytokines analyzed in the oral cavity and serum of leukoplakia patients, and that VEGF levels in saliva correlate highly with levels in oral rinse and serum. Further, high levels of IL-8 and VEGF in leukoplakia patients are easily analyzed by ELISA techniques and provide additional data for our growing database on potential salivary biomarker use in oral cancer diagnostics.