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

Abstract

Abstract. 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.

The High Costs of Low-Grade Inflammation: Persistent Fatigue as a Consequence of Reduced Cellular-Energy Availability and Non-adaptive Energy Expenditure

“…In addition to its function for sleep, melatonin can also act as an antioxidant and immune regulator, playing a role in mitochondrial DNA protection (Ramis et al, 2015 ). Studies in rodents confirm that inflammation and stress are capable of modulating melatonin levels (Persengiev et al, 1991 ; Huang et al, 2014 ) and that melatonin can reduce inflammation and oxidative stress associated with sleep deprivation (Kim et al, 2012 ; Zhang et al, 2013 ). However, melatonin administration may be insufficient to restore sleep-wake rhythmicity (Mirmiran and Pevet, 1986 ).…”

Depressive symptoms, quality of sleep, and disease control in women with asthma

“…In fact, negative effects of insufficient sleep on pulmonary function were previously described in patients with chronic obstructive pulmonary disease [37]. In experimental animals, sleep deprivation can exacerbate acute lung inflammation, an effect that can be attenuated by melatonin, which has a powerful antioxidant action [38]. Interestingly, nocturnal melatonin administration can reportedly improve the quality of sleep in women with mild to moderate stable asthma [12].…”

Sleep Problems in Chronic Inflammatory Diseases: Prevalence, Treatment, and New Perspectives: A Narrative Review

“…It acts as a reactive oxygen species neutralizer and apoptosis inhibitor and might block the expression of NF-κB, TNF [ 182 ]. In a study on a mice model of the lung, inflammation melatonin was able to lower the level of IL-6 and TNF in animals administered with lipopolysaccharide and subjected to SD [ 183 ]. Another study on sleep-deprived mice with IBD yielded similar results [ 182 ].…”