Sleep and circadian disruption reshape immune homeostasis in oral tissues: mechanistic roles of melatonin and cortisol in periodontal disease and xerostomia.

Sleep disturbance has emerged as a major modifier of immune homeostasis in chronic inflammatory diseases, yet its immunological relevance to oral tissues remains incompletely integrated. Accumulating evidence indicates that sleep and oral inflammatory diseases are linked through coordinated neuroendocrine-immune pathways, with melatonin and cortisol constituting a central circadian hormonal axis that shapes immune balance. Melatonin, predominantly secreted during the nocturnal phase, exerts antioxidant, anti-inflammatory, and immunomodulatory effects that support periodontal immune homeostasis and salivary gland function. In contrast, sleep disruption and chronic activation of the hypothalamic-pituitary-adrenal axis led to dysregulated cortisol secretion, promoting immune suppression, microbial dysbiosis, and progressive periodontal tissue breakdown. Experimental, observational, and clinical studies consistently associate poor sleep quality with suppressed melatonin rhythms, elevated cortisol levels, and increased prevalence of periodontitis and xerostomia, while sleep disorders such as obstructive sleep apnea further exacerbate oral inflammatory vulnerability through both circadian and mechanical mechanisms. Despite these associations, the causal immune pathways linking circadian hormonal dysregulation to oral disease progression remain insufficiently defined. This review synthesizes current mechanistic and clinical evidence to conceptualize the melatonin-cortisol axis as an immunoregulatory bridge between disturbed sleep and oral inflammatory disease, and discusses its implications for biomarker development and immune-informed therapeutic strategies.