Fingolimod Attenuates Lung Injury after Diffuse Brain Injury

Abstract

Abstract One of the severe and common extracranial injuries associated with severe traumatic brain injury (TBI), such as diffuse brain injury (DBI), is acute lung injury (ALI). The inflammatory reaction plays a key role in ALI development. Fingolimod inhibits multiple inflammatory responses. We hypothesized that fingolimod administration could attenuate ALI by modulating the inflammatory reaction secondary to TBI. Fingolimod was administered for 3 consecutive days after DBI. Immunohistochemistry and hematoxylin and eosin staining were performed for histopathological evaluation to assess the degree of inflammatory cell infiltration and ALI after DBI. Pulmonary edema and capillary leakage were quantified by assessing the lung wet-to-dry ratio and Evans blue dye leakage. Western blotting was used to assess the concentrations of inflammatory factors, blood–air barrier tight junction proteins, and apoptosis proteins in lung tissue after DBI. Flow cytometry was used to analyze the peripheral blood Treg content and to evaluate the changes in peripheral immunity after DBI. It was found that DBI induced significant lung injury and caused changes in the peripheral blood Treg content. Fingolimod treatment significantly alleviated lung barrier injury and reduced inflammatory cytokine production, inflammatory cell infiltration, apoptotic protein levels, and the wet/dry weight ratio in lung tissue 3 days after DBI, accompanied by an increase in the peripheral blood Treg content. Thus, it was found that DBI can result in significant pulmonary damage accompanied by significant inflammatory responses. Fingolimod reduced the inflammatory response and alleviated DBI-induced lung injury, providing a potential new approach for the treatment of ALI in DBI.