Active Hexose Correlated Compound Activates Immune Function to Decrease Chlamydia trachomatis Shedding in a Murine Stress Model

Abstract

A cold-induced stress mouse model for investigating chlamydia genital infection and immune response analysis was established in our laboratory. Previous results showed that cold-induced stress results in suppression of the immune response and increased intensity of chlamydia genital infection in the mouse model. The purpose of the present study was to evaluate the potential therapeutic value of active hexose correlated compound (AHCC) against chlamydia genital infection in mice. AHCC is an extract of mushroom commonly used as a dietary supplement is known to boost the immune system. Mice were infected intravaginally with Chlamydia trachomatis after a 24-day cold-stress application. Oral administration of AHCC to stressed or non-stressed mice was carried out seven days before infection and during the course of infection along with cervicovaginal swabbing. Cytokine production by peritoneal and splenic T cells isolated from AHCC-fed stressed mice and non-stressed mice was measured ELISA. Splenic T cells from both animal groups were co-cultured with mouse monocyte J774.2 cell line or cultured by addition of supernatants of AHCC-treated J774.2 cell line for 24 hours. Infection studies showed that AHCC-feeding compared to phosphate buffered saline (PBS)-feeding to stressed mice resulted in reduced Chlamydia trachomatis shedding from the genital tract. Levels of tumor necrosis factor-alpha (TNF-α) and interleukin 6 (IL-6) were significantly increased in stressed mice receiving AHCC compared to stressed mice receiving PBS. Production of interferon gamma (IFN-γ) and interleukin 2 (IL-2) in the AHCC group was significantly high compared to production in PBS-fed group. Splenic T cells from stressed and non-stressed cultured with supernatants of AHCC-treated J774.2 cell line resulted in significantly increased TNF-α or IFN-γ production. Results obtained in this study show that AHCC improves the function of immune cells as indicated by the restoration of levels of cytokines production that were suppressed under cold induced-stress conditions. This is the first report showing that oral administration of AHCC enhances the function of the immune system, which could result in increased resistance of the host to chlamydia genital infection.This is an open

The Effects of AHCC®, a Standardized Extract of Cultured Lentinura edodes Mycelia, on Natural Killer and T Cells in Health and Disease: Reviews on Human and Animal Studies

“…We recently reported the promotion of Th 1 and 17 cells, which predominantly produced IFN-γ and IL-17, respectively, by AHCC® through inducing IL-1β production from monocytes in humans [20]. In accordance with this 3 Journal of Immunology Research finding, the culture supernatants of AHCC®-treated murine monocytic J744.2 cells promoted the production of TNF-α from splenic T cells of mice [12] while AHCC® induced IL-8 production from human myelocytic THP-1 cells via activating mitogen-activated protein kinases (MAPKs) and NF-κB pathways [14]. In a mouse study, AHCC® administration increased cytokine production in the intestine fluid dependently of TLR2 and TLR4, suggesting the implication of these molecules in AHCC®-mediated immune modulation [52].…”

“…Of the oligosaccharides in AHCC®, about 20% are α-1,4-glucans, of which a proportion is partially acylated, with a mean molecular weight around 5000 Daltons [6,7]. The effects of AHCC® on immune cells of humans and animals were reported in in vitro and in vivo studies, suggesting the possible help of its supplementation in defending the host against infections and malignancies via modulating the immune system [6,[9][10][11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28]. This review focuses on the reported effects of AHCC® on natural killer (NK) and T cells given their roles in host defense and inflammation [29][30][31][32][33][34], providing a platform for the better understanding of immune-mediated mechanisms and clinical implications of AHCC® and possibly other medical mushrooms in health and disease.…”

Active hexose-correlated compound enhances extrinsic-pathway-mediated apoptosis of Acute Myeloid Leukemic cells

“…Because AHCC can activate monocytes and monocytic cell lines [13,26,27] and because AML blasts are immature myeloid-lineage cells, we sought to determine whether AHCC could directly affect blast-cell survival and proliferation. We began by testing AHCC against the MV4-11 cell line, which contains the FLT3-ITD mutation shared by approximately 20% of AML patients [28] and is linked to increased risk of relapse and mortality [29].…”

“…For example, it prolongs survival in advanced liver cancer patients [19], enhances the antitumor activity of 5-fluorouracil [41], and reduces tumor burden alone and in combination with CpG oligodeoxynucleotides in a murine melanoma model [17]. It shows immune-modulatory effects as well such as serving to sooth hapten-induced colitis in rats [42], to decrease bacterial burden [43], and to enhance resistance to pathogens such as Chlamydia trachomatis in murine models of stress [26]. As such, AHCC may not only aid in the clearance of AML blasts, it may also help reduce the incidence of infections in these typically immune-compromised patients.…”

“…After one week, mice received either AHCC (600 mg/kg) mixed into PBS, or PBS control by gavage twice per week for 2 weeks. Similar doses of AHCC were used previously as daily treatments with no evidence of toxic effects [13,14,25,26]. Gavage was performed by using a plastic feeding tube (Instech Laboratories, Inc, Plymouth Meeting, PA).…”