Table 4.
Immunomodulatory effects related to cancer: in vivo studies.
| Preparation | Experimental Model | Key Findings | References |
|---|---|---|---|
| Extract from Coriolus versicolor (Cov 1 strain) | Pre-injection in LPS-treated rats and PBMCs isolated—100 mg/kg, i.p. | Partially prevents endotoxin tolerance through maintaining febrile response; increases IL-6 and greater NF-κB activation in response to LPS stimulation ex vivo; enhances mitogenic effect of LPS and increases ROS generation. | Jedrzejewski et al. 2019 [95] |
| Glucan—home-made purification—[→6)-α-D- Glcp-(1→]n. | Sarcoma 180-bearing mice—100 or 200 mg/kg for nine days, subcutaneously | Promotes the secretion of IL-2, −4, −6, −10, −17A and IFN-α and -γ; enhances cytokine production associated with T-helper Th2 and Th17 cells; effect dependent on IL-10. | Awadasseid et al. 2017 [96] |
| PSP | C57BL/6 male mice—50 mg/kg, p.o. | When combined with acacia gum, increased total IgG titre levels (day 4) while decreasing IgM titre had no effect on IgA or IgE titre levels. | Sekhon et al. 2016 [97] |
| Protein-bound polysaccharides (PBP) | Fever-range hyperthermia (FRH) combined with PBP in rats—100 mg/kg i.p. | Combination treatment of (FRH + PBP) decrease IL-1β, IL-6 and TNF-α mRNA expression in peripheral blood mononuclear cells; see Table 3 for in vitro effect. | Pawlikowska et al. 2016 [78] |
| PSP | Male Wistar rats—100 mg/kg, i.p. 2 h before LPS | Increases the duration of endotoxin fever; increases the blood level of IL-6 (3 or 14 h post-injection); effect inhibited by anti-IL-6 antibody (30 µg/rat). | Jedrzejewski et al. 2015 [98] |
| PSP | 500 mg/kg/d by p.o. in mice for 25 days | Decreases the mean weights of tumors; increases thymus index and spleen index relative in tumour-bearing C57BL/10J (TLR4+/+) mice but not in C57BL/10ScCr (TLR4−) mice; see Table 3 for in vitro effect. | Wang et al. 2015 [81] |
| PSP | Male Wistar rats—50, 100 and 200 mg/kg, i.p. | Induces a rapid reduction in temperature; elevates TNF-α level; anti-TNF-α antibody abolish effect on temperature. | Jedrzejewski et al. 2014 [99] |
| Aqueous extract | Mouse mammary carcinoma 4T1 tumor bearing mice—1 g/kg, p.o. for 4 weeks | Increases IL-2, 6, 12, TNF-α and IFN-γ productions from the spleen lymphocytes; see Table 1 and Table 2 for other effects | Luo et al. 2014 [23] |
| PSK | As an adjuvant to OVAp323-339 vaccine in vivo—DC activation 1000 µg—one injection by intradermal route | Enlarges draining lymph nodes with higher number of activated DC; stimulates the proliferation of OVA-specific T-cells, and induces T-cells that produce multiple cytokines (IFN-γ, IL-2, and TNF-α; see Table 3 for in vitro effect. | Engel et al. 2013 [84] |
| PSK | PSK with docetaxel- mouse prostate tumor (TRAMP-C2) cells injected orthotopically—docetaxel (5 mg/kg) injected i.p. twice weekly; PSK (300 mg/kg) daily by oral gavage or combination for 11–13 days | Lower level of decrease in number of white blood cells than docetaxel alone; increases numbers of tumor-infiltrating CD4+ and CD8+ T-cells; PSK with or without docetaxel enhance mRNA expression of IFN-γ—no effect on T-regulatory FoxP3 mRNA expression in tumors; augments the docetaxel-induced splenic natural killer cell cytolytic activity against YAC-1 target cells. | Wenner et al. 2012 [51] |
| PSK | Neu transgenic mice received subcutaneous implant of 1 million MMC cells—100 mg/kg, p.o. 3 times per week for up to 4 weeks | Potentiates the anti-tumour effect of anti-HER2/neu mAb therapy in neu-T mice; see Table 3 for in vitro effect. | Lu et al. 2011 [87] |
| Methanol extract of fruiting body of Serbian origin | C57BL/6 mice inoculated with syngeneic B16 tumor cells—50 mg/kg, i.p. for 14 days | Peritoneal macrophages collected 21 days after tumor implantation possess stronger tumouristatic activity ex vivo than those from untreated animals; see Table 1 and Table 2 for other effects. | Harhaji et al. 2008 [31] |
| PSP—composed of 90% polysaccharides (74.6% glucose, 2.7% galactose, 1.5% mannose, 2.4% fucose and 4.8% xylose) and 10% peptides (18 different amino acids, mostly aspartic acid and glutamic acid) | Acetic acid-induced writhing model—0.2–2 μmol/kg, i.p. in hot-plate test; 2–4 μmol/kg, i.p. in acetic acid-induced writhing response; 0.05–4 μmol/kg, i.p. induction of writhing response by itself. | Decreased the number of acetic acid-induced writhing by 92.9%; PSP itself induces a dose-dependent writhing response; increased the release of PGE2, TNF-α, IL-1β, and histamine in mouse peritoneal macrophages and mast cells both in vivo and in vitro (1–100 μM). | Chan et al. 2006 [100] |
| Purified polysaccharide (CV-S2-Fr.I) of C. versicolor obtained by Sepharose CL-6B gel chromatography | Mouse peritoneal macrophage—100 µg/mL | Enhanced macrophage lysosomal enzyme activity by 250%; enhances the induction of NO production by interferon-γ (no effect by its own). | Jeong et al. 2006 [101] |
| PSP | Tumour bearing mice—radiation (8 Gy/mouse) or with PSP, i.p. 5 days before implantation and for 10 days after | Increases natural killer cell, lymphocyte and granulocyte counts in blood and spleen; no direct tumor reducing effect; see Table 1 for direct cytotoxic effect. | Mao et al. 2001 [102] |
| PSP | C57BL/6NIA mice—diets containing 0.1, 0.5 or 1.0% PSP for 1 month | No effect on mitogenic response to Con A, PHA or LPS, or on production of IL-1, IL-2, IL- 4 and PGE2; induced higher delayed-type hypersensitivity response (1.0% PSP) in old but not in young mice. | Wu et al. 1998 [103] |
| Small polypeptide of about 10 Kd | Human tumour cells (SMMU-7721 or LS174-T) inculated into nude mice—2 mg, i.p. for 2 weeks. | Increases WBC and IgG levels; decreases the incidence of tumor mass. | Yang et al. 1992 [48] |
Abbreviations: Con A, concanavalin A; IFN-γ, interferon-γ; LPS, lipopolysaccharide; NO, nitric oxide; PGE2, prostaglandin E2; PHA, phytohemagglutinin; WBC, white blood cell.