In addition to GM-CSF and MIP-1β (not measured in healthy volunteers after low doses AndoSan™ consumption), in patients with IBD, IL-1β, IL-2, IL-6, IL-17 and G-CSF were detected in reduced concentrations after mushroom intake both among healthy volunteers and patients. Thus, both pro-inflammatory cytokines (IL-1β, IL-6) and chemokines (IL-8, MIP-1β, MCP-1, GM-CSF, G-CSF) were downregulated by AndoSan™ in these patients with IBD. The three cytokines with the most marked reduction in LPS-stimulated blood from these
patients were MIP-1β, IL-1β and IL-6. Chemokine MIP-1β belongs to the family of macrophage inflammatory 1 proteins, which orchestrate acute and chronic inflammatory responses at sites of injury or infection mainly by recruiting pro-inflammatory Staurosporine supplier cells [32]. selleck chemicals llc Recently, an unselective increase in chemokine expression in mucosa has been demonstrated by immunohistochemistry
among patients with UC and CD. Such studied chemokines include MIP1-β, MCP-1 and IL-8 [19], which were reduced in collected blood from patients with UC (MIP1-β, MCP-1) and CD (MIP1-β, IL-8). IL-6 in the intestinal mucosa is synthesized by mononuclear cells [21, 24], and it is elevated in serum in both UC [25] and CD [24]. We observed a considerable decline in this cytokine (Fig. 2B) in patients with UC after consumption of the mushroom extract. Similar to our study (Tables 1–3), increased serum levels of IL-1β are seldom detected [24], but IL-1β levels are elevated [20, 33, 34] in intestinal lesions in both UC and CD. Interestingly, levels of IL-1β in LPS-stimulated blood declined in both diseases, again pointing to a net anti-inflammatory effect of AndoSan™. The hitherto unreported reduction in pleiotropic IL-17 (Fig. 3F) in patients with CD is intriguing [35]. Because IL-17 will both convey a host defensive mechanism to various extracellular bacterial Sclareol infections and pathogenic involvement in autoimmune disease, a reduced concentration of this cytokine may dampen these inflammatory reactions. The general tendency in patients with UC and CD was that cytokine levels
were either significantly or insignificantly reduced after 12 days of mushroom consumption. Thus, the lack of significant reduction in concentrations especially for cytokines TNF-α, IFN-γ and IL-6 (CD) could be because of the limited number of patients included in each IBD group (type II error). For cytokines IL-4, IL-5, IL-7 and IL-13 in patients with IBD, there were no striking alterations in their concentrations throughout the experimental period. None of the Th2 cytokines (IL-4, -5, -13) potentially relevant for UC seemed to be initially elevated or modulated by AndoSan™, whilst IL-2 was the only Th1 cytokine that was reduced after AndoSan™ ingestion in patients with CD. According to the Th2/Th1 dichotomy [36], one could also have anticipated an inverse increase in Th2 and Th1 cytokines in UC and CD, respectively.