Creatine Supplementation Augments Chronic Allergic Airway Inflammation and Remodelling: from Mice to Human Evidence

Creatine supplementation exacerbates asthma phenotype, but the cellular mechanisms involved in this response are unknown. Forty-Eight C57Bl/6 male mice (n = 2 x 6 mice/group) were distributed into Control (Co), Creatine (Cr), Ovalbumin (OVA) and Ovalbumin+Creatine (OVA+Cr) groups. A chronic model of ovalbumin (OVA)-induced asthma was used, when sensitization was done by using i.p. injections of OVA (400µg/mouse) on days 0, 14, 28 and 42 and aerosol challenge by using OVA solution (1%), 3x/week, from 21st-53rd day. Creatine supplementation (Cr; 0.5 g/kg/day) was administered from 21st-53rd day. Additionally, human cells, BEAS-2B, total leukocytes, eosinophils and CD4+ T lymphocytes were primed with IL-4 (1h prior Cr) and supplemented with Cr (10mM) for 4 hours. The in vivo study revealed that Cr increases total proteins, ATP levels, total cells, eosinophils and IL-5 and IL-13 levels in bronchoalveolar lavage (BAL), as well as IL-4, IL-5 and IL-13 levels in supernatant of re-stimulated mediastinal lymph nodes (MLN). Cr also increased the accumulation of collagen fibers on airway wall and mucus production. Immunohistochemistry (IHC) study revealed that Cr induced airway epithelial and peribronchial leukocytes activation. Under Cr stimuli, human (BEAS-2B, total leukocytes, eosinophils and CD4+ T cells) responded to increased release of ATP, TNF-alpha, IL-6 and IL-8. Creatine supplementation increases asthma phenotype through activation of airway epithelial cells and peribronchial leukocytes.