ORIGINAL ARTICLE Effects of a-glucans from Agaricus bisporus on ex vivo cytokine production by LPS and PHA-stimulated PBMCs; a placebo-controlled study in slightly hypercholesterolemic subjects JJ Volman 1 , RP Mensink 1 , LJLD van Griensven 2 and J Plat 1 1 Department of Human Biology, NUTRIM School for Nutrition, Toxicology and Metabolism, Maastricht University Medical Centre þ , Maastricht, The Netherlands and 2 Plant Research International, Wageningen University, Wageningen, The Netherlands Introduction: Mushrooms are known for their immune modulating effect for which the polysaccharide fraction, mainly glucans, seem to be responsible. Fungal b-glucans have been studied extensively, whereas little is known about mushroom a-glucans. We have earlier shown that the polysaccharide fraction from the mushroom A. bisporus, consisting 90% of a-glucans, induced in vitro tumor necrosis factor (TNF)a and nitric oxide production. The purpose of this study was to evaluate the effects of consuming. Method: A. bisporus a-glucan on ex vivo cytokine production by human peripheral mononuclear blood cells (PBMCs). A double- blind randomized trial was designed in which 56 mildly hypercholesterolemic subjects consumed a control fruit juice with no added a-glucans (200 ml/day) for a 2-week run-in period. For the next 5 weeks, the control group (N ¼ 30) continued consumption of the control fruit juice, whereas the intervention group (N ¼ 26) consumed the same fruit juice enriched with a-glucans from A. bisporus (5 g glucans/day). Changes in interleukin (IL)-1b, IL-6 and TNFa cytokine production by lipopolysaccharide (LPS)-stimulated PBMCs were evaluated, as well as changes in T-helper (Th)1/Th2 cytokines by phytohemaggutinin (PHA)-stimulated PBMCs. Results: Consumption of A. bisporus a-glucans lower LPS-induced TNFa production by 69% (P ¼ 0.017) as compared with the control group, whereas no effect on IL-1b and IL-6 was observed. No obvious Th1–Th2 skewing by PHA-stimulated PBMCs was observed. However, we observed a trend towards a decreased production of IL-12 and IL-10. Conclusion: Our current finding suggests that in vivo, a-glucans have lost their efficacy to stimulate the immune response as observed in our in vitro mouse model. European Journal of Clinical Nutrition advance online publication, 3 March 2010; doi:10.1038/ejcn.2010.32 Keywords: Agaricus bisporus; a-glucan; cytokines; immune modulation; nutrition; peripheral mononuclear blood cell Introduction Mushrooms have been studied extensively for their immune- modulating and anti-tumor properties (Brown et al., 2003; Borchers et al., 2004; Lull et al., 2005; Chen and Seviour, 2007; Wei et al., 2008). Indeed, there are many potentially biologically active compounds present in mushrooms, for example, small proteins, lectins, polyphenols and poly- saccharides. It is assumed that the polysaccharides are a main bioactive part of the mushrooms, at least in relation to their immune-modulating effects (Wasser, 2002). These poly- saccharides are mainly b-glucans that are present in the cell walls. In addition, also a-glucans are present in the polysaccharide fraction of mushrooms (Zhang and Cheung, 2002). Whereas the effects of b-glucans have been studied extensively, little is known about the immune-modulating effect of mushroom a-glucans. We have reported earlier that a polysaccharide fraction from Agaricus bisporus, which contained 90% a-glucan increased nitric oxide and tumor Received 13 September 2009; revised 13 November 2009; accepted 11 January 2010 Correspondence: Dr J Plat, Department of Human Biology, Maastricht University Medical Centre þ , Nutrition and Toxicology Institute Maastricht (NUTRIM), PO Box 616, Maastricht NL-6200 MD, The Netherlands. E-mail: J.Plat@hb.unimaas.nl European Journal of Clinical Nutrition (2010), 1–7 & 2010 Macmillan Publishers Limited All rights reserved 0954-3007/10 $32.00 www.nature.com/ejcn