ORIGINAL CONTRIBUTION Pro-inflammatory effects of the mushroom Agaricus blazei and its consequences on atherosclerosis development Juliana L. Gonc ¸alves • Eric H. Roma • Ana Cristina Gomes-Santos • Edenil C. Aguilar • Daniel Cisalpino • Luciana R. Fernandes • Ange ´lica T. Vieira • Dirce R. Oliveira • Valbert N. Cardoso • Mauro M. Teixeira • Jacqueline I. Alvarez-Leite Received: 2 September 2011 / Accepted: 21 October 2011 / Published online: 16 November 2011 Ó Springer-Verlag 2011 Abstract Purpose Extracts of the mushroom Agaricus blazei (A. blazei) have been described as possessing immuno- modulatory and potentially cancer-protective activities. However, these effects of A. blazei as a functional food have not been fully investigated in vivo. Methods Using apolipoprotein E-deficient (ApoE -/- ) mice, an experimental model of atherosclerosis, we eval- uated the effects of 6 or 12 weeks of A. blazei supple- mentation on the activation of immune cells in the spleen and blood and on the development of atherosclerosis. Results Food intake, weight gain, blood lipid profile, and glycemia were similar between the groups. To evaluate leukocyte homing and activation, mice were injected with 99m Tc-radiolabeled leukocytes, which showed enhanced leukocyte migration to the spleen and heart of A. blazei- supplemented animals. Analysis of the spleen showed higher levels of activation of neutrophils, NKT cells, and monocytes as well as increased production of TNF-a and IFN-c. Circulating NKT cells and monocytes were also more activated in the supplemented group. Atherosclerotic lesion areas were larger in the aorta of supplemented mice and exhibited increased numbers of macrophages and neutrophils and a thinner fibrous cap. A. blazei-induced transcriptional upregulation of molecules linked to mac- rophage activation (CD36, TLR4), neutrophil chemotaxy (CXCL1), leukocyte adhesion (VCAM-1), and plaque vulnerability (MMP9) were seen after 12 weeks of supplementation. Conclusions This is the first in vivo study showing that the immunostimulatory effect of A. blazei has proathero- genic repercussions. A. blazei enhances local and systemic inflammation, upregulating pro-inflammatory molecules, and enhancing leukocyte homing to atherosclerosis sites without affecting the lipoprotein profile. Keywords A. blazei Á Diet Á Atherosclerosis Á Inflammation Á ApoE -/- mice Background Extracts from the mushroom Agaricus blazei (A. blazei) have been reported to be medicinal [1] and have been studied for their immunostimulatory effects [2–5]. Among these effects are the induction of nitric oxide (NO) secre- tion in murine macrophages [5] and transcriptional upreg- ulation of cytokines such as IL-8, IL-6, IL1-b, IL2, and TNF-a [6, 7]. These effects can be ascribed to the high concentration of proteoglycans and b-glucans, important J. L. Gonc ¸alves Á E. H. Roma Á A. C. Gomes-Santos Á E. C. Aguilar Á L. R. Fernandes Á A. T. Vieira Á M. M. Teixeira Á J. I. Alvarez-Leite (&) Department of Biochemistry and Immunology, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais 31270-901, Brazil e-mail: jalvarezleite@gmail.com D. Cisalpino Department of Microbiology, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais 31270-901, Brazil D. R. Oliveira Department of Basic Nursing, Faculty of Nursing, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais 30130-100, Brazil V. N. Cardoso Department of Clinical and Toxicological Analysis, Faculty of Pharmacy, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais 31270-901, Brazil 123 Eur J Nutr (2012) 51:927–937 DOI 10.1007/s00394-011-0270-8