The present study was to ascertain the immunomodulating and anti-tumor effects of Ganoderma (G.) lucidum. Polysaccharides (PS) from fresh fruiting bodies of G. lucidum (PS-G) were isolated and used to potentiate cytokine production by human monocytes-macrophages and T lymphocytes. Our results had shown that the levels of interleukin (IL)-1b, tumor necrosis factor (TNF)-a, and IL-6 in macrophage cultures treated with PS-G (100 mg/ml) were 5.1-, 9.8-and 29-fold higher, respectively, than those of untreated controls. In addition, the release of interferon (IFN)-g from T lymphocytes was also greatly promoted in the presence of PS-G (25-100 mg/ml). Furthermore, these cytokine-containing mononuclear cell-conditioned media (PSG-MNC-CM) were found to suppress the proliferation and clonogenicity of both the HL-60 and the U937 leukemic cell lines. DNA labeling and gel electrophoresis showed that treatment with PSG-MNC-CM markedly induced leukemic-cell apoptosis. Flow-cytometric analysis revealed that few (2.3 6 0.8%) apoptotic cells were seen in the control cultures, while PSG-MNC-CM treatment resulted in a significant increase in the apoptotic population both in the HL-60 (38.3 6 4.5%) and in the U937 (44.5 6 3.8%) cells. In addition, 40 to 45% of the treated leukemic cells were triggered to differentiate into mature monocytic cells expressing CD14 and CD68 surface antigens. However, PS-G alone had no such effects even at a higher dose of 400 mg/ml. Since untreated macrophages and T lymphocytes produced little or no cytokine, and normal MNC-CM did not suppress leukemic cell growth, it was suggestive that the anti-tumor activity of PSG-MNC-CM was derived from the elevated levels of cytokines. Antibody-neutralization studies further revealed that the anti-tumor cytokines in the PSG-MNC-CM were mainly of TNF-a and IFN-g, and these 2 cytokines acted synergistically on the inhibition of leukemic-cell growth. Int. J. Cancer 70:699-705, 1997.

Differentiation therapy with all‐trans retinoic acid (ATRA) represents a landmark approach in the treatment of acute promyelocytic leukemia (APL). However, a potentially fatal complication of retinoic acid (RA) syndrome occurs in about a quarter of patients and its pathophysiology is still unclear. In order to investigate whether or not the treatment with ATRA leads to increased elaboration of inflammatory cytokines and adhesion molecules by the APL cells, the expression of interleukin (IL)‐1β, tumor necrosis factor (TNF)‐α, IL‐8, L‐selectin and intercellular adhesion molecule‐1 (ICAM‐1) was examined in the APL cells after induction of differentiation with ATRA in the presence or absence of granulocyte‐colony stimulating factor (G‐CSF) or IL‐3 in the present study. Cytokine elaboration by the treated cells was detected using both Northern blotting and enzyme‐linked immunosorbent assay. Our results have shown that ATRA induces an increased expression of IL‐8, IL‐1β, TNF‐α and ICAM‐1 in APL cells, which can be amplified by the addition of G‐CSF. These data imply that the induction of inflammatory cytokines in APL cells may play an important role in the pathogenesis of RA syndrome. Furthermore, G‐CSF, through its potent differentiating activity, may increase the risk of such complications during ATRA treatment.

SummaryIn March 2018, an abortion storm caused by porcine reproductive and respiratory syndrome virus was confirmed in a farrow‐to‐finish pig herd in Taiwan. Open reading frame 5 and non‐structural protein 2 of the virus confirmed that the virus is closely related to the virulent strains circulating in the United States.

The granulomonopoietic enhancing factor (GM-EF) is a novel myelopoietic regulator produced by human monocyte-derived lipid-containing macrophages (MDLMs). In the present study, we examined the effect of lymphocytes on GM-EF production by preincubation of MDLMs with various preparations of lymphocyte subpopulations in cell-mixed and in double agar layer cultures. Our results showed that a cell concentration-dependent suppression of GM-EF production was noted in cultures with mitogen-activated T cells, and mitogen-activated/resting B cells, while those containing resting T cells had no such effect. Thus, GM-EF production in the presence of 1 x 10(5)/ml activated T cells or activated/resting B cells was greatly reduced to 5% or 20%, respectively. The lymphocyte-induced suppression was evident in both cell-mixed and double layer cultures, implying that the effector cells might exert their influences via mediators. Assay for cytokine activity revealed that a high level (648.2-685.2 pg/ml) of tumor necrosis factor-alpha (TNF-alpha) was found in MDLM cultures with resting/activated B cells, and in those with activated T cells high levels of both TNF-alpha (510.5 pg/ml) and interferon-gamma (IFN-gamma) (321.3 pg/ml) could be detected, whereas in cultures with MDLMs and/or resting T cells, these cytokines were not measurable. Treatment of MDLMs with either recombinant (r) TNF-alpha or rIFN-gamma invariably resulted in a dose-dependent decrease in GM-EF production with intense suppression at doses between 400-800 U/ml.(ABSTRACT TRUNCATED AT 250 WORDS)