Pathway and Decreases Capillary Damage but Not Neutrophil Recruitment in IL-1/LPS- Insufflated Rats

Background Glutamine (GLN) attenuates acute lung injury (ALI) but its effect on alveolar macrophages is unknown. We hypothesized that GLN pretreatment would induce the anti-inflammatory CD163/heme oxygenase (HO)-1/p38-MAPK dephosphorylation pathway in alveolar macro-phages and reduce ALI in rats insufflated with interleukin-1 (IL-1) and lipopolysaccharide (LPS). Methods Male Sprague-Dawley rats were randomized to the following groups: GLN-IL-1/LPS-, GLN +IL-1/LPS-, GLN-IL-1/LPS+, and GLN+IL-1/LPS+. GLN pretreatment was given via gavage (1g/kg L-alanyl-L-glutamine) daily for 2 days. ALI was subsequently induced by insufflating 50ng IL-1 followed by 5mg/kg E.coli LPS. After 24h, bronchoalveolar lavage (BAL) protein, lactate dehydrogenase (LDH) and neutrophil concentrations were analyzed. BAL alveolar macrophage CD163+ expression, HO-1 and p38-MAPK concentrations were measured, as well as alveolar macrophage tumor necrosis factor (TNF)-α and interleukin (IL)-10 concen-trations. Histology and immunofluorescence studies were also performed. Results Following IL-1/LPS insufflation, GLN pretreated rats had significantly decreased BAL pro