Enhancement of rat hepatic macrophages by treatment with interleukin-2 and streptococcal preparation OK432, with reference to antitumor activity, soluble factor production and Ia expression

Abstract

The effect of biological response modifiers, such as interleukin-2 (IL-2) and streptococcal preparation OK432, on the functions of hepatic macrophages was investigated. The macrophages, even with no exogenous stimulation, produced superoxide anion (O2-) and tumor necrosis factor (TNF), displayed cytotoxicity against K562 cells and cytostasis against P815 cells and expressed immune-region-associated antigen (Ia). IL-2 administered in vitro or in vivo enhanced O2- production by hepatic macrophages and the intravenous injection of OK432 also enhanced O2 production. Furthermore, IL-2 added to the culture medium of hepatic macrophages isolated from OK432-injected rats augmented O2- production even more. The TNF production and Ia expression of the macrophages were also increased by the intravenous injection of OK432. As with O2- production, the cytotoxicity of the cells was enhanced by OK432 injection or by IL-2 added to the culture medium and the combination of OK432 and IL-2 augmented their cytotoxicity even more. Thus, the present study suggested that IL-2 and OK432 induce the augmentation of the antitumor activity of hepatic macrophages, partly as a result of the increase in production of O2- and TNF and Ia expression.

Intestinal Ischemia and the Gut–Liver Axis: An in Vitro Model

“…Ogle et al showed that KC's are responsible for the increased levels of TNF-␣ and IL-6 in trauma, hemorrhagic shock, and resuscitation [26,27]. Decreasing the number or functional ability of KC's can lead to decreased levels of inflammatory cytokines, as seen in models of hepatic resection and cecal ligation or puncture [28,29]. We have previously demonstrated that modulation of KC function has a direct effect on cytokine release in rats with superior mesenteric artery occlusion [30].…”

Systemic administration of liposome‐encapsulated OK‐432 prolongs the survival of rats with hepatocellular carcinoma through the induction of IFN‐γ‐producing hepatic lymphocytes

“…It augments the activity of macrophages, lymphocytes and natural killer (NK) cells, 2 and induces multiple cytokines including interleukin (IL)‐1, 3 IL‐2, 3 IL‐6, 4 tumor necrosis factor (TNF)‐α 5 and interferon (IFN)‐γ 6,7 . In clinical studies and animal experiments, OK‐432 has been found to augment these activities in peripheral blood lymphocytes (PBL), 8 pleural effusion lymphocytes, 9 splenic lymphocytes and hepatic macrophages 10,11 . However, it has not been specifically reported in hepatic lymphocytes.…”

Activated peritoneal macrophages inhibit the proliferation of rat ascites hepatoma AH-130 cells via the production of tumor necrosis factor- α and nitric oxide

“…Thus, it is possible that TNF-a and NOx produced from activated macrophages are interacting to exert the anti-proliferative activity against AH-130 cells. It is known that LPS-or IL-2-activated macrophages secretes superoxide anions that have cytotoxic effect on tumor cells [8,35,36]. To examine the involvement of superoxide anions in the anti-tumor activity against AH-130 cells, we added superoxide dismutase and catalase to coculture of AH-130 cells and LPS-or IL-2-activated peritoneal macrophages.…”