The association of Candida and antifungal therapy with pro-inflammatory cytokines in oral leukoplakia

Abstract

Objectives: To study the association of Candida and antifungal therapy with pro-inflammatory cytokines (PIC) in oral leukoplakia (OL).

Materials and methods: A prospective observational study where immunocompetent adult subjects with OL (30 homogenous (HL), 30 non-homogenous (NHL)) and 30 age and sex-matched healthy controls (C) with no predisposing factors for oral Candida infection were recruited. Sterile cotton swabs and ophthalmic sponges were used to sample the lesion surface in OL and buccal mucosa in C, for direct microscopy and culture for Candida and to determine levels of PIC (IL-6, IL-8. IL-17, TNF-α) by ELISA, respectively. Sampling for PIC was repeated at same sites in OL, 2 weeks after antifungal therapy.

Results: Candida was associated with 55.3% of NHL, 23.3% of HL and 13.3% of C. The oral secretary levels of PIC were raised in NHL as compared to HL and C. The levels of IL-6, IL-8, TNF-α (p<0.001) and IL-17 (p<0.01) were significantly raised in Candida positive NHL while IL-6 (p<0.05) and TNF-α (p<0.01) were significantly raised in Candida positive HL before antifungal treatment. After antifungal treatment, there was significant reduction in PIC in Candida positive NHL and HL.

Conclusions: Candida infection contributes to the inflammatory milieu in Candida associated OL which increases the risk of carcinogenesis. Antifungal therapy reduces the PIC in Candida associated OL.

Clinical relevance: Identification and elimination of predisposing factors for Candida infection, like cessation of harmful habits, maintenance of oral/denture hygiene, surveillance for Candida and antifungal therapy at intervals, are recommended in OL.

Clinical trial registration: ClinicalTrials.gov Identifier: NCT04712929.

Keywords: Antifungal agents; Candida; IL-17; IL-6; IL-8; Oral leukoplakia; Pro-inflammatory cytokines; TNF alpha.