Cold stress provokes lung injury in rats co-exposed to fine particulate matter and lipopolysaccharide

Cold exposure aggravates respiratory diseases, which are also influenced by the exposures to particulate matter and endotoxin in the air. The aim of this study was to investigate the potential interactions among cold stress, fine particulate matter (PM2.5, particles with aerodynamic diameter of 2.5 mu m or less) and lipopolysaccharide (LPS, pure chemical form of endotoxin) on rat lung and to explore the related possible mechanisms of the interactions. Wistar rats were randomly grouped to be exposed to, 1) normal saline (0.9% NaCl), 2) PM2.5, 3) LPS, and 4) PM2.5 and LPS (PM2.5 + LPS) through intratracheal instillation under cold stress (0 degrees C) and normal temperature (20 degrees C). Lung function, lung tissue histology, inflammatory response and oxidative stress levels were measured to examine the lung injury and to investigate the potential mechanisms. Exposure to PM2.5 or LPS substantially changed pulmonary function [indicated by peak inspiratory flow (PIF) and peak expiratory flow (PEF)], inflammatory cytokine levels [indicated by interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha)] and lung histology, compared to the non-exposed groups. Exposure to PM2.5 + LPS under cold stress induced the most significant changes, including the increases of IL-6, TNF-alpha and thiobarbituric acid-reactive substances (TBARS), the decreases of PIF and PEF and more severe lung injury, among all exposure scenarios. Glutathione peroxidase activity and, nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) were found to be suppressed under cold stress, whereas Nrf2 and HO-1 levels were observed to be upregulated by exposure to PM2.5 or LPS under normal temperature. In conclusion, cold stress may aggravate the lung injury in rats induced by simultaneous exposure to PM2.5 and LPS. The progress may involve the suppressing of Nrf2/HO-1 signal pathway.