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Creatine Supplementation Exacerbates Allergic Lung Inflammation and Airway Remodeling in Mice

Departments of ¹ Pathology, ² Physical Therapy, and ³ Clinical Medicine, School of Medicine; and ⁴ Biomedical Engineering Laboratory, Escola Politécnica, University of São Paulo, São Paulo, Brazil

Correspondence and requests for reprints should be addressed to Marisa Dolhnikoff, M.D., Ph.D., Departamento de Patologia, Faculdade de Medicina da Universidade de São Paulo, Av. Dr. Arnaldo, 455 – 2° Andar – Sala 2118, 01246-903, São Paulo, SP, Brazil. E-mail: maridol{at}usp.br

Creatine supplement is the most popular nutritional supplement, and has various metabolic functions and sports medicine applications. Creatine supplementation increases muscle mass and can decrease muscular inflammation. Some studies have also suggested a beneficial role of creatine supplementation on chronic pulmonary diseases such as chronic obstructive pulmonary disease and cystic fibrosis. Among athletes, the prevalence of asthma is high, and many of these individuals may be taking creatine. However, the effects of creatine supplementation on chronic pulmonary diseases of allergic origin have not been investigated. In the present study, we analyzed the effects of creatine supplementation on a model of chronic allergic lung inflammation. Thirty-one Balb/c mice were divided into four groups: control, creatine (Cr), ovalbumin (OVA), and OVA+Cr. OVA and OVA+Cr groups were sensitized with intraperitoneal injections of OVA on Days 0, 14, 28, and 42. OVA challenge (OVA 1%) and Cr treatment (0.5 g/kg/d) were initiated on Day 21 and lasted until Day 53. We determined the index of hyperresponsiveness, the serum levels of OVA-specific immunoglobulin (Ig)E and IgG₁, and the total and differential cell counts in bronchoalveolar lavage fluid. We also quantified airway inflammation, and the airway density of IL-4+, IL-5+, IL-2+, IFN-+, and insulin-like growth factor (IGF)-1+ cells, collagen and elastic fibers, and airway smooth muscle thickness. Our results showed that creatine in OVA-sensitized mice increased hyperresponsiveness; eosinophilic inflammation; airway density of IL-4+, IL-5+, and IGF-1 inflammatory cells; airway collagen and elastin content; and smooth muscle thickness. The results show that creatine supplementation exacerbates the lung allergic response to OVA through a T helper cell type 2 pathway and increased IGF-1 expression.

Key Words: creatine supplementation • asthma • lung inflammation • Th2 cytokines • insulin-like growth factor-1

CLINICAL RELEVANCE We show for the first time that creatine supplementation exacerbates the effects of ovalbumin sensitization (airway inflammation, remodeling, and hyperresponsiveness) in mice, suggesting that creatine might have deleterious effects in individuals with asthma.

 

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