Protective effect of oxytocin on LPS-induced acute lung injury in mice

Xiaona An,Jianbo Wu,Xiaomei Yang,Hongli Chen,Xiaotong Sun,Yonghao Hou,Peng Zhang

doi:10.1038/s41598-019-39349-1

Abstract

Oxytocin (OT), a neurohypophyseal hormone synthesized in the paraventricular and supraoptic nuclei of the hypothalamus, has been reported to have an anti- inflammatory effect. However, its role in acute lung injury (ALI) has never been investigated. The aim of this study was to explore the therapeutic effects and potential mechanism action of OT on lipopolysaccharide (LPS)-induced ALI. Mice were treated with OT 30 min before the intraperitoneal injection of LPS. After 2 h, the effects of OT on lung histopathological changes, lung wet/dry (W/D) ratio, myeloperoxidase (MPO) activity, levels of inflammatory cytokines in the bronchoalveolar lavage fluid (BALF), and expression of inflammation proteins were detected. The results showed that OT significantly reduced LPS-induced pathological injury, W/D ratio, MPO activity, and the levels of interleukin (IL)-1β, IL-18 and IL-6. Further, OT also inhibited LPS-induced Toll-like receptor 4 expression and NLR family pyrin domain containing 3 inflammasome activation. OT receptor antagonist (L-368,899) was given 90 min before injecting OT to further demonstrate the role of OT in LPS-induced ALI. The results showed OT could not alleviate the aforementioned inflammatory reactions after administering L-368,899. In conclusion, the present results indicated that OT could reduce inflammatory responses of LPS-induced ALI.

Highlights

Acute lung injury (ALI) is a critical illness syndrome with a high mortality rate of 40–60%1
The pathological changes were detected using hematoxylin and eosin (HE) staining to investigate the protective effects of OT on LPS-induced acute lung injury (ALI)
L-368,899 significantly exacerbates inflammation compared LPS group. These results suggested that oxytocin’s anti-inflammatory effects were possible due to its binding to OT receptors (OTRs), because the anti-inflammatory effects on LPS-induced ALI were effectively blocked by the OTR antagonist L-368,899

Summary

Introduction

Acute lung injury (ALI) is a critical illness syndrome with a high mortality rate of 40–60%1. ALI is characterized by refractory hypoxemia and progressive dyspnea. It is most often seen as part of a systemic inflammatory process. LPS can activate the host receptor TLR4 and trigger an inflammatory response, resulting in ALI4,5. An effective anti-inflammatory drug used to reduce lung injury was urgently needed. Oxytocin (OT), a neurohypophyseal hormone synthesized in the paraventricular and supraoptic nuclei of the hypothalamus, has a wide range of effects in the body. It exerts its functions via G protein–coupled receptors[6]. This study aimed to evaluate the anti-inflammatory effects and mechanism of action of oxytocin on LPS-induced ALI in a mouse model

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Conclusion