Immunohematopoietic modulation by oral β-1,3-glucan in mice infected with Listeria monocytogenes.
In this study we demonstrated that the oral administration of β-1,3-glucan (Imunoglucan®) protects mice from a lethal dose of Listeria monocytogenes (LM) when administered prophylactically for 10 days at the doses of 150 and 300 mg/kg, with survival rates up to 40%. These doses also prevented the myelosuppression and the splenomegaly caused by a sublethal infection with LM, due to increased numbers of granulocyte-macrophage progenitors (CFU-GM) in the bone marrow. Investigation of the production of colony-stimulating factors revealed an increased colony-stimulating activity (CSA) in the serum of infected mice pre-treated with Imunoglucan®. The treatment also restored the reduced ability of stromal cells to display myeloid progenitors in long-term bone marrow cultures (LTBMC) and up-regulated IL-6 and IL-1α production by these cells in the infected mice, which was consistent with higher number of non-adherent cells. Additional studies to investigate the levels of interferon-gamma (INF-γ) in the supernatant of splenocyte cultures demonstrated a further increase in the level of this cytokine in infected-treated mice, compared to infected controls. In all cases, no differences were observed between the responses of the two optimal biologically effective doses. In contrast, no significant changes were produced by the treatment with the 50mg/kg dose. In addition, no changes were observed in normal mice treated with the three doses used. All together our results suggest that orally given Imunoglucan® indirectly modulates immune activity and probably disengages Listeria induced suppression of these responses by inducing a higher reserve of myeloid progenitors in the bone marrow in consequence of biologically active cytokine release (CSFs, IL-1α, IL-6, and INF-γ).
Departamento de Farmacologia/Hemocentro, Faculdade de Ciências Médicas, Universidade Estadual de Campinas (UNICAMP), Campinas, SP, Brazil.
Cristiane O
CO
Torello
Julia
J
de Souza Queiroz
Sueli C
SC
Oliveira
Mary L S
ML
Queiroz
D000276:Adjuvants, Immunologic / Q000008:administration & dosage / Q000627:therapeutic use*; D000284:Administration, Oral; D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D018929:Cell Culture Techniques; D002478:Cells, Cultured; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000097:blood; D055014:Granulocyte-Macrophage Progenitor Cells / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D006410:Hematopoiesis / Q000187:drug effects* / Q000276:immunology*; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D007371:Interferon-gamma / Q000276:immunology / Q000378:metabolism; D053582:Interleukin-1alpha / Q000096:biosynthesis / Q000276:immunology; D015850:Interleukin-6 / Q000096:biosynthesis / Q000276:immunology; D008089:Listeria monocytogenes / Q000187:drug effects; D008088:Listeriosis / Q000150:complications / Q000276:immunology / Q000382:microbiology / Q000517:prevention & control*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D013163:Splenomegaly / Q000209:etiology / Q000276:immunology / Q000517:prevention & control; D047071:beta-Glucans / Q000008:administration & dosage / Q000627:therapeutic use*
D000276:Adjuvants, Immunologic; D053582:Interleukin-1alpha; D015850:Interleukin-6; D047071:beta-Glucans; D007371:Interferon-gamma; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; C033363:beta-1,3-glucan