Salivary and Serum Cytokbioine Levels in Oral Chronic Graft-Versus-Host Disease: A Longitudinal Study on the Role of IL-6, IL-1α, and IL-17

Background: Chronic graft-versus-host disease (cGVHD) is a significant complication following hematopoietic cell transplantation, often manifesting with oral lesions that severely impact quality of life. Cytokines such as IL-6, IL-1α, and IL-17 are implicated in inflammation and may serve as biomarkers for disease activity and therapeutic response in cGVHD. Methods: A prospective monocentric study was conducted on 10 patients with oral cGVHD at San Paolo Hospital, Milan, between April 2023 and January 2024. Salivary and serum levels of IL-6, IL-1α, and IL-17 were measured pre- and post- topical clobetasol treatment for the oral mucosa using enzyme-linked immunoassay (ELISA). Patients underwent clinical assessments for oral pain and dryness using visual analog scales (VAS) and the Oral Mucositis Rating Scale (OMRS). Wilcoxon and Spearman correlation tests were used for statistical analysis. Results: Significant reductions in serum IL-17 (p = 0.006) and trends towards reduced salivary IL-6 (p = 0.066) were observed post-treatment. No significant changes were found in IL-1α levels. Clinical assessments showed significant improvement in pain and OMRS scores post-therapy (p < 0.05). No correlation was found between cytokine levels and clinical symptoms. Conclusions: While IL-6 and IL-17 play roles in cGVHD, only IL-17 showed significant reduction after topical steroid therapy. This suggests IL-17's potential as a marker for inflammatory activity in cGVHD. Serum IL-17 may serve as a useful biomarker in oral cGVHD. Future studies with larger cohorts are needed to further validate these findings and explore the role of salivary cytokines in disease monitoring.