High MW hyaluronan inhibits smoke inhalation‐induced lung injury and improves survival

Background and objective: High MW hyaluronan (HMW HA) as opposed to low MW hyaluronan (LMW HA) has been shown to have anti‐inflammatory and anti‐apoptotic effects. We hypothesized that treatment with HMW HA would block smoke inhalation lung injury by inhibiting smoke‐induced lung inflammation and airway epithelial cell apoptosis. Methods: Anesthetized, intubated male rats were randomly allocated to either control or smoke inhalation injury groups. Rats were treated with 3‐mL subcutaneous normal saline solution (sham) or LMW HA (35 kDa) or HMW HA (1600 kDa) 18 h before exposure to 15 min of cotton smoke (n = 5 each). Rats were also treated post smoke inhalation with 1600 kDa HA by intra‐peritoneal injection (3 mL) or intra‐tracheal nebulization (200 µL). Lung neutrophil infiltration, airway apoptosis, airway mucous plugging and lung injury were assessed 4 h after smoke inhalation injury. Results: Rats pretreated with 1600 kDa HA had significantly less smoke‐induced neutrophil infiltration, lung oedema, airway apoptosis and mucous plugging. Pretreatment with 35 kDa HA, in contrast, increased smoke‐induced neutrophil infiltration and lung injury score. Intra‐tracheal administration of a single dose 1600 kDa HA, but not intra‐peritoneal injection, significantly improved survival post smoke inhalation. Conclusions: High MW hyaluronan (1600 kDa) may prove to be a beneficial therapy for smoke inhalation through inhibition of smoke‐induced inflammation, lung oedema, airway epithelial cell apoptosis and airway mucous plugging.