Mangiferin, a C-glucosylxanthone (1,3,6,7-tetrahydroxyxanthone-C2-β-D-glucoside) purified from plant sources was shown to have in vivo growth-inhibitory activity against ascitic fibrosarcoma in Swiss mice. Following in vivo or in vitro treatment, it also enhanced tumor cell cytotoxicity of the splenic cells and peritoneal macrophages of normal and tumor-bearing mice. In vitro treatment of the splenic cells of tumor-bearing mice with mangiferin resulted in augmented killing of tumor cells, both resistant and sensitive to natural killer cells. Mangiferin was also found to antagonize in vitro the cytopathic effect of HIV. The drug appears to act as a potent biological response modifier with antitumor and antiviral effect.

~Two new glycowithanolides, sitoindoside IX (1) and sitoindoside X (Z), isolated from Withuniu somniferu Dun., were evaluated for their immunomodulatory and CNS effects (anti-stress, memory and learning) in laboratory animals, because the plant extract is used by practitioners of the Indian systems of medicine for similar purposes. The two compounds, in doses of 100-400 & n o u s e , produced statistically significant mobilization and activation of peritoneal macrophages, phagocytosis and increased activity of the lysosomal enzymes secreted by the activated macrophages. Both these compounds (50-200 mg/kg p.0.) also produced significant anti-stress activity in albino mice and rats and augmented learning acquisition and memory retention in both young and old rats. These findings are consistent with the use of W . somniferu, in Ayurveda, to attenuate cerebral function deficits in the geriatric population and to provide non-specific host defence.

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Hippadine, an alkaloid of the Amaryllidaceae, produced reversible inhibition of fertility in male rats. A decrease in the testicular weight and DNA content and an increase in protein concentration indicated a fall in the relative proportion of freshly divided cells. The weights of accessory sex organs revealed continued production of androgens. A plausible mechanism for this biochemical function of hippadine is envisaged.

The chemokines macrophage inflammatory protein 1 alpha (MIP 1 alpha), interleukin-8 (IL-8) and RANTES are potent regulators of leukocyte trafficking. Examination of chemokine secretion by human peripheral blood lymphocytes after stimulation with anti-CD3 or phorbol 12, 13 myristate acetate and ionomycin showed CD8+ cells were the dominant source of MIP 1 alpha and RANTES. Although production of MIP 1 alpha and IL-8 were similar in pharmacologically stimulated CD4+ CD45RA+, CD4+ CD45RO+, and CD8+ CD45RA+ cells, the largest amounts of MIP 1 alpha and RANTES were secreted by CD8+ CD45RO+ lymphocytes. A parallel pattern of prolonged chemokine mRNA expression for at least 18 h after activation was observed in the T cells subsets. These results confirm that human T lymphocytes have a unique capacity for secretion of these three chemokines. In addition, CD8+ cells have an unrecognized role in recruiting cells to sites of inflammation, and adult human CD45RA+ cells have a physiologically significant secretory capacity.

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The involvement of PRL in regulating monocyte/macrophage functions is suggested by the presence of PRL-Rs in these cells. Here, we show that PRL, though it failed to activate mouse peritoneal resident macrophages (RMs), acted as a second signal and activated mouse peritoneal inflammatory macrophages (EMs) to a tumoricidal state. The cytotoxicity of mouse tumor-associated macrophages (TAMs) isolated at day 1 of tumor (Ehrlich ascites carcinoma, EAC) growth was enhanced by PRL. However, with progression of tumor growth, TAMs became nonresponsive to the hormone.