Psychological stress enhances keloid development via stress hormone-induced abnormal cytokine profiles and inflammatory responses

Abstract

Keloid is a fibroproliferative disorder resulting from the abnormal wound healing process, and it causes both cosmetic concerns and functional disabilities. Genetic predisposition, wound trauma, foreign body reaction, mechanical stretch, and immune dysfunction are common risk factors, but there remain mechanisms unclarified, leaving challenges in addressing the clinical concerns of recurrence and resistance. However, similar patterns of growth and metabolism between keloids and cancers provide a unique insight into the future exploration of keloid pathogenesis. Psychological stress has been demonstrated to be involved in the development and drug resistance of multiple cancers, but this aspect remains less-explored in keloids. Clinical observations and published investigations have noticed that persistent stress is common among keloid patients and their symptoms tend to deteriorate under stressful conditions. Following a thorough review of the published literature, we have identified three signaling pathways that might imply how stress hormones are likely to influence the keloid pathogenesis via activating adrenergic receptors and dysregulating the immune system. Thus, we hypothesized that psychological stress would be a key risk factor for keloid development via stimulating fibrosis, aggravating local hypoxia, and inflammation.