Melatonin improves inflammatory cytokine profiles in lung inflammation associated with sleep deprivation

Sleep disturbance has become an endemic behavior in modern countries, and its prevalence has also increased. Even a subtle sleep deficiency is related to health problems. Particularly, patients with pulmonary disease often complain of insomnia. We recently showed that sleep deprivation (SD) exacerbates existing acute lung inflammation, and that melatonin treatment attenuates it via anti-apoptotic and anti-oxidant action. In order to reinforce our previous report, the present study was designed to evaluate pro-inflammatory mediators in acute lung inflammation in SD mice. In addition, we investigated the infiltration of inflammatory cells into the lungs. Twenty-five ICR mice were divided into 5 groups (n=5/group): control, SD, lipopolysaccharide (LPS), LPS + SD and LPS + SD + melatonin. The SD mice were deprived of sleep for 96 h in a multiplatform water bath. LPS (5 mg/kg) and melatonin (5 mg/kg) were administered on day 2. The mice were sacrificed on day 3, and serum and bronchoalveolar lavage (BAL) fluid were collected. The serum levels of inflammatory cytokines were increased in the LPS + SD group. Interleukin-6, tumor necrosis factor-α and interferon-γ levels were also increased in BAL fluid in the LPS + SD group. Melatonin reduced inflammatory mediators in the serum and BAL fluid. The accumulation of leukocytes in the LPS and LPS + SD mice was elevated, however, melatonin inhibited the recruitment of inflammatory cells (p<0.05). Lymphocytes in the BAL fluid of the LPS + SD group were increased, and macrophage levels were decreased; however, the increment was attenuated by melatonin administration (p<0.05). In conclusion, this study indicates that melatonin has a protective effect against lung inflammation associated with SD.