Stress dysregulates plasma cytokines during human mucosal healing

Objective: Stress is known to alter immune function important in the protection from infection and wound healing. Our previous studies have demonstrated impaired mucosal wound healing during examination stress. In this study, we sought to determine whether stress altered the expression of inflammatory cytokines in plasma during mucosal wound healing.

Methods: 65 professional students had experimental wounds placed during stress (i.e., academic examinations) and a nonstress period (summer vacation). Two wounds were placed on the hard palates at each time: a 3.5 mm circular wound and a 1 x 5 mm longitudinal wound. The 3.5 mm wound was videographed daily and measured by photoplanimetry. The 1 x 5 mm wound was biopsied 6 or 24 hours later. Each person was biopsied at the same interval during the stress and nonstress time. Blood was drawn just before wounding and plasma was stored frozen until protein levels of 20 analytes were measured using multiplex analysis.

Results: During the examination time, individuals reported significantly more perceived stress, state anxiety and tension (p<0.001) than the same students during summer vacation. Students had significantly larger wounds 24 hours after wounding during the stress period (p<0.05). IL-1b, IL-6, IL-10, and IFN-a were significantly (p<0.05) reduced in unstimulated plasma, while the levels of IL-1a, IL-8, IFN-g, and IP-10 approached significant reductions (p<0.10). In biopsied tissue 6 hours after wounding mRNA levels of Il-1b, Il-6, and IL-8 were significantly increased during the stress period. 24 hours after wounding tissue mRNA levels of these cytokines were not decreased by stress.

Conclusion: In the systemic circulation, higher levels of inflammatory markers are may indicate a system able to respond more quickly and efficiently to an immune challenge such as wounding. Stress impairment of immune function results in more inflammation at the wound site and impaired healing. Supported by NIH/NIDCR RO1DE12792.