Inhibition of human monocyte-macrophage and lymphocyte cytotoxicity to herpes simplex-infected cells by glucan.

The effect of short term in vitro incubation of glucan--a reticuloendothelial system stimulator--on subsequent cytotoxicity of human monocyte-macrophages (MP) and lymphocytes (L) to Herpes simplex virus-infected cells in a 51Cr-release assay was analyzed. Particulate, cell-associated glucan irreversibly inhibited MP antibody-dependent cellular cytotoxicity (ADCC). In contrast, the inhibition of L-ADCC and L-natural killer cytotoxicity could be reversed by dissociation of glucan and cells utilizing serum gradient centrifugation, a process which did not remove the glucan. These experiments reveal further basic differences between MP and L-ADCC using the reagent glucan.

Glucan-induced keratoderma in acquired immunodeficiency syndrome.

Six of 20 patients with acquired immunodeficiency syndrome (AIDS) or AIDS-related complex receiving intravenous infusions of soluble glucan (beta-1-3 polyglucose) developed a keratoderma of the palms and soles. The eruption began during the first two weeks of therapy and resolved two to four weeks after its discontinuation. The eruption was different in appearance from our previously reported keratoderma blennorrhagica in AIDS-associated psoriasis. None of the other 735 patients with AIDS or AIDS-related complex not treated with soluble glucan developed a similar keratoderma. The correlation between receiving glucan and the hyperkeratosis is highly significant. Since glucan is a naturally occurring component of the cell walls of yeast, fungus, and some bacterial organisms, recognition of its ability to induce such a striking reaction pattern may be of general significance and interest, although the reaction itself may be limited to patients with AIDS.

Immunochemotherapy of bladder carcinoma with glucan and cyclophosphamide.

Recent evidence suggests a role for both immunotherapy and chemotherapy in the treatment of transitional cell carcinoma. Glucan, a derivative of the cell wall of Saccharomyces cerevisiae and a potent immunostimulant, was used in combination with cyclophosphamide for treatment of implanted murine transitional cell carcinoma (MBT 2). Cyclophosphamide prevented tumor appearance when tumor burden was low and decreased tumor growth rate in larger tumor volumes, but was unable to eradicate established tumors. Glucan did not reduce tumor incidence but decreased animal mortality. These experimental observations may correlate well with clinical evidence and suggest future clinical use of these agents.

Soluble polyglycans enhance recovery from cobalt-60--induced hemopoietic injury.

Six soluble polyglycans (glucan-C, glucan-F, glucan-S, krestin, lentinan, and schizophyllan), two soluble polymannans (mannan-A and mannan-R), and one soluble polyfructan (levan) were assayed for their ability to enhance hemopoietic recovery in C3H/HeN mice when administered either 1 h before or 1 h after a 6.5-Gy dose of cobalt-60 radiation. Hemopoietic recovery was measured by the endogenous spleen colony assay and was compared with recovery in both radiation control mice and irradiated mice treated with glucan-P (a particulate polyglycan previously shown to enhance recovery from radiation-induced hemopoietic injury). Compared with radiation controls, when administered before irradiation, mannan-A, glucan-F, and glucan-S enhanced endogenous colony formation 4.2-5.1-fold (equivalent to glucan-P), and levan and schizophyllan approximately 2.7-fold. Lentinan, krestin, mannan-R, and glucan-C did not enhance hemopoietic recovery above radiation controls under these conditions. When polyglycan administration was delayed until after irradiation, endogenous colony formation was enhanced 3.0-3.9-fold by mannan-A, schizophyllan, glucan-S, krestin, and glucan-F (at least comparable with glucan-P) but not at all by mannan-R, levan, lentinan, or glucan-C.

Development of a bioassay for anti tumor activity of biological response modifiers of the reticuloendothelial stimulant class: reproducibility of the bioassay.

Intravenously administered DiLuzio glucan, Wellcome C. parvum, and Glaxo BCG caused dose dependent increases in the tumor cell loss from the lungs of C57BL/6J and DBA/2J mice challenged respectively with intravenous 125IuDR labelled B16 or T 1699 mammary carcinoma cells. The results were reproducible with respect to the optimal doses and the magnitudes and shapes of the dose response curves.