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Published ahead of print on July 19, 2007, doi:10.1165/rcmb.2007-0108OC

Am. J. Respir. Cell Mol. Biol., Volume 37, Number 6, December 2007, 660-667

A more recent version of this article appeared on December 1, 2007
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Submitted on March 28, 2007
Revised on July 18, 2007

Creatine Supplementation Exacerbates Allergic Lung Inflammation and Airway Remodeling in Mice

Rodolfo P Vieira1, Anna Cecilia S. Duarte2, Renata C Claudino2, Adenir Perini3, Angela B. G. Santos1, Henrique T Moriya4, Fernanda M Arantes-Costa3, Milton A Martins3, Celso R. F. Carvalho2, and Marisa Dolhnikoff1*

1 Department of Pathology, University of Sao Paulo, School of Medicine, Sao Paulo, Brazil, 2 Department of Physical Therapy, University of Sao Paulo, School of Medicine, Sao Paulo, Brazil, 3 Department of Clinical Medicine, University of Sao Paulo, School of Medicine, Sao Paulo, Brazil, 4 University of Sao Paulo, Escola Politecnica, Biomedical Engineering Laboratory, Sao Paulo, Brazil

* To whom correspondence should be addressed. 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 COPD 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 in four groups: Control, Creatine (Cr), ovalbumin (OVA), and OVA+Cr. OVA and OVA+Cr groups were sensitized with i.p. injections of OVA on days 0, 14, 28 and 42. OVA challenge (OVA 1%) and Cr treatment (0.5g/kg/day) were initiated on day 21 until day 53. We determined the index of hyperresponsiveness, the serum levels of OVA-specific IgE and IgG1, and the total and differential cell counts in BALF. We also quantified airway inflammation, and the airway density of IL-4+, IL-5+, IL-2+, IFN-gamma+ and 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 Th2 pathway and increased IGF-1 expression.







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