Modulation of proinflammatory cytokines and leukocyte mobilization by melatonin in response to sterile tissue injury in Wistar albino rats

OBJECTIVE: To test the hypothesis that the neurohormone, melatonin, differentially activates the release of the proinflammatory cytokines, such as, interleukin-1 beta (IL-1beta) and tumor necrosis factor-alpha (TNF-alpha), as well as inducing leukocyte mobilization into the peripheral blood in response to a sterile tissue injury.

METHODS: This study was conducted between November 2011 and September 2012 at the Department of Physiology, College of Medicine, King Khalid University, Abha, Kingdom of Saudi Arabia. Sterile tissue injury of either skin injury or gastric ulceration was induced in equal numbers in Wistar albino rats aged 7-8 weeks (150-200 g) (20 each), with each group being equally divided into melatonin treated or vehicle-treated.

RESULTS: Melatonin treatment and sterile tissue injuries significantly (p<0.05) increased the plasma levels of IL-1beta and TNF-alpha compared to baseline levels. However, higher levels of IL-1beta compared with TNF-alpha were obtained only with melatonin treatment. Furthermore, melatonin treatment significantly increased (p<0.05) total leukocyte counts before the induction of skin injury and gastric ulceration, and remained elevated for a longer period than injured, but vehicle-treated rats. In addition, our methods of inducing skin injury or gastric ulceration caused an increase in leukocyte levels in the blood circulation (p<0.05).

CONCLUSION: Melatonin differentially stimulated plasma IL-1beta and TNF-alpha, and increased blood leukocyte counts before and after sterile tissue injuries. It is worth pursuing further investigation into the therapeutic effect of melatonin in inflammatory disease that involves leukocyte recruitment to sites of injury.