An immunostimulatory extract based on the medicinal mushroom Agaricus blazei Murill (AbM) has been shown to stimulate mononuclear phagocytes in vitro to produce pro‐inflammatory cytokines, and to protect against lethal peritonitis in mice. The present aim was to study the effect of AbM on release of several cytokines in human whole blood both after stimulation ex vivo and in vivo after oral intake over several days in healthy volunteers. The 17 signal substances examined were; T helper 1 (Th1) cytokines [interleukin (IL)‐2, interferon (IFN)‐γ and IL‐12], T helper 2 cytokines (IL‐4, IL‐5 and IL‐13), pleiotropic (IL‐7, IL‐17), pro‐inflammatory [IL‐1β, IL‐6, tumour necrosis factor (TNF)‐α (mainly produced by Th1 cells)] – and anti‐inflammatory (IL‐10) cytokines, chemokines [IL‐8, macrophage inhibitory protein (MIP)‐1β and monocyte chemoattractant protein (MCP)‐1] and leukocyte growth factors [granulocyte colony‐stimulating factor (G‐CSF), granulocyte/macrophage colony stimulating factor]. After stimulation of whole blood ex vivo with 0.5–5.0% of a mushroom extract, AndoSan™ mainly containing AbM, there was a dose‐dependent increase in all the cytokines studied, ranging from two to 399‐fold (TNF‐α). However, in vivo in the eight volunteers who completed the daily intake (60 ml) of this AbM extract for 12 days, a significant reduction was observed in levels of IL‐1β (97%), TNF‐α (84%), IL‐17 (50%) and IL‐2 (46%). Although not significant, there was a trend towards reduced levels for IL‐8, IFN‐γ and G‐CSF, whilst those of the remaining nine cytokines tested, were unaltered. The discrepant results on cytokine release ex vivo and in vivo may partly be explained by the antioxidant activity of AbM in vivo and limited absorption of its large, complex and bioactive β‐glucans across the intestinal mucosa to the reticuloendothelial system and blood.

An immunomodulatory extract (AndoSan™) based on the medicinal mushroom Agaricus blazei Murill (AbM) has shown to reduce blood cytokine levels in healthy volunteers after 12 days’ ingestion, pointing to an anti‐inflammatory effect. The aim was to study whether AndoSan™ had similar effects on cytokines in patients with ulcerative colitis (UC) and Crohn’s disease (CD). Calprotectin, a marker for inflammatory bowel disease (IBD), was also measured. Patients with CD (n = 11) and with UC (n = 10) consumed 60 ml/day of AndoSan™. Patient blood plasma was harvested before and after 6 h LPS (1 ng/ml) stimulation ex vivo. Plasma and faecal calprotectin levels were analysed using ELISA and 17 cytokines [IL‐2, IFN‐γ, IL‐12 (Th1), IL‐4, IL‐5, IL‐13 (Th2), IL‐7, IL‐17, IL‐1β, IL‐6, TNF‐α, IL‐8, MIP‐1β, MCP‐1, G‐CSF, GM‐CSF and IL‐10] by multiplex assay. After 12 days’ ingestion of AndoSan™, baseline plasma cytokine levels in UC was reduced for MCP‐1 (40%) and in LPS‐stimulated blood for MIP‐1β (78%), IL‐6 (44%), IL‐1β (41%), IL‐8 (30%), G‐CSF (29%), MCP‐1 (18%) and GM‐CSF (17%). There were corresponding reductions in CD: IL‐2 (100%), IL‐17 (55%) and IL‐8 (29%) and for IL‐1β (35%), MIP‐1β (30%), MCP‐1 (22%), IL‐8 (18%), IL‐17 (17%) and G‐CSF (14%), respectively. Baseline concentrations for the 17 cytokines in the UC and CD patient groups were largely similar. Faecal calprotectin was reduced in the UC group. Ingestion of an AbM‐based medicinal mushroom by patients with IBD resulted in interesting anti‐inflammatory effects as demonstrated by declined levels of pathogenic cytokines in blood and calprotectin in faeces.

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These results support that oral intake of AndoSan™ exhibits an anti-inflammatory effect in humans in vivo.

Surgery, even modern minimal invasive laparoscopic surgery, induces an initial inflammatory and acute phase response which is followed by a period of immunosuppression rendering surgical patients more susceptible to infection. Here, we aimed to study changes in monocyte inflammatory responses and inflammatory modulation mechanisms following laparoscopic colorectal surgery for colon cancer. Blood samples were collected from 19 colon cancer patients before, directly after and daily for 3 days following surgery. Blood cells were exposed ex vivo to bacterial lipopolysaccharide (LPS) or the inflammatory modulator 9-cis retinoic acid (9cisRA). In blood samples taken prior to surgery, we found significant pro-inflammatory responses to LPS, indicating classical monocyte activation. Directly after surgery, LPS induced significantly less early pro-inflammatory cytokines and monocyte/granulocyte-attracting chemokines. The LPS-mediated release of interleukin (IL)-1β was still significantly attenuated 3 days after surgery. In patient monocytes collected after surgery, we found increased levels of suppressors of cytokine signaling (SOCS)1 and SOCS3 mRNA, reported to be associated with polarization towards resolving macrophages. The retinoic acid isomer 9cisRA, reported to attenuate LPS-mediated inflammatory responses and alter chemokine responses in cultured monocytes, had a similar effect in patient blood. Three days after surgery, 9cisRA still attenuated pro-inflammatory responses, but the induction of monocyte chemoattractive protein (MCP)-1/CCL2 mRNA in monocytes was reduced. This study indicates changes in monocyte responses that last for at least 3 days after laparoscopic surgery.