Sleep deprivation (SD) is an epidemic phenomenon
in modern countries, and its harmful effects are well known. SD
acts as an aggravating factor in inflammatory bowel disease.
Melatonin is a sleep-related neurohormone, also known to have
antioxidant and anti-inflammatory effects in the
gastrointestinal tract; however, the effects of melatonin on
colitis have been poorly characterized. Thus, in this study, we
assessed the measurable effects of SD on experimental colitis
and the protective effects of melatonin. For this purpose, male
imprinting control region (ICR) mice (n=24) were used; the mice
were divided into 4 experimental groups as follows: the control,
colitis, colitis with SD and colitis with SD and melatonin
groups. Colitis was induced by the administration of 5% dextran
sulfate sodium (DSS) in the drinking water for 6 days. The mice
were sleep-deprived for 3 days. Changes in body weight,
histological analyses of colon tissues and the expression levels
of pro-inflammatory cytokines and genes were evaluated. SD
aggravated inflammation and these effects were reversed by
melatonin in the mice with colitis. In addition, weight loss in
the mice with colitis with SD was significantly reduced by the
injection of melatonin. Treatment with melatonin led to high
survival rates in the mice, in spite of colitis with SD. The
levels of pro-inflammatory cytokines, such as interleukin (IL)-1β,
IL-6, IL-17, interferon-γ and tumor necrosis factor-α, in the
serum of mice were significantly increased by SD and reduced by
melatonin treatment. The melatonin-treated group showed a
histological improvement of inflammation. Upon gene analysis,
the expression of the inflammatory genes, protein kinase Cζ (PKCζ)
and calmodulin 3 (CALM3), was increased by SD, and the levels
decreased following treatment with melatonin. The expression
levels of the apoptosis-related inducible nitric oxide synthase
(iNOS) and wingless-type MMTV integration site family, member 5A
(Wnt5a) genes was decreased by SD, but increased following
treatment with melatonin. Treatment with melatonin reduced
weight loss and prolonged survival in mice with colitis with SD.
Melatonin exerted systemic anti-inflammatory effects. Gene
analysis revealed a possible mechanism of action of melatonin in
inflammation and sleep disturbance. Thus, melatonin may be
clinically applicable for patients with inflammatory bowel
disease, particulary those suffering from sleep disturbances.