Production of Interleukin-1 Activity of Kupffer Cells from Mice Treated with the Acidic Mannan Fraction of Bakers' Yeast.

Abstract

Kupffer cells (KC), 1) resident macrophages of the liver, comprise a large and functionally important part of the mononuclear phagocyte system. Interleukin 1 (IL-1) is a monokine with a broad spectrum of biological activities, and its effects on a variety of cell types have been established. There are several reports that suggest that IL-1 could serve as a therapeutic tool for patients and mice with bacterial and fungal infections. [2][3][4][5][6] There is also accumulating evidence that lipopolysaccharide (LPS)-stimulated KC produce IL-1 or IL-1-like factors.7-12) However, the role of KC, which could be an important source of these mediators, has not been completely evaluated to date.We have reported that an acidic mannan fraction (WAM025) of bakers' yeast confers significant protection against the ascites forms of Ehrlich, sarcoma 180, and Meth A tumors, 13) and Candida albicans infections 14) in mice. Until now, there have been few reports of the production of IL-1 from phagocytes by mannan, except for our previous report that polymorphonuclear leukocytes (PMN) in peritoneal exudate cells, but not macrophages, of mice administered WAM025 produced larger amounts of IL-1. 15) In this study, we describe the production of IL-1 activity by KC treated with WAM025 in vivo and in vitro to clarify further the antitumor and infection-protective mechanisms. MATERIALS AND METHODSMice Specific pathogen-free (SPF) male BALB/c mice, 5 to 6 weeks old, were obtained from the Shizuoka Laboratory Animal Center, Hamamatsu, Japan. Preparation of Mannan FractionsThe mannan subfractions were prepared as previously reported.16) Briefly, the bulk mannan fraction extracted from the parent bakers' yeast, a wild-type strain of the Saccharomyces cerevisiae cells, was fractionated by DEAE-Sephadex A-50 column chromatography, and the neutral and the strongly acidic fractions, which were eluted with water and 0.25 M NaCl (designated as WNM and WAM025, respectively), were used in this study.Treatment of Mice The mice were intraperitoneally (i.p.) administered the mannan fraction (WNM or WAM025) at a dose of 150 mg/kg/d for 5 d.Preparation of KC The KC were prepared by a method based on that of Hashimoto et al.17) Briefly, the liver was perfused with 0.2% Pronase E (Kaken Pharmaceutical), then the small fragments were digested for 20 min in the same solution at 37°C. After the incubation, 0.5 mg of deoxyribonuclease (DNase) type I (Merck) was added to digest the cellular debris. After 2 repeated 20 min-DNase treatments, the KC were then separated by Percoll (Pharmacia) gradient centrifugation (density 1.080). The KC were washed three times with Hanks balanced salt solution and suspended in 10% FBS-RPMI-1640 medium. The KC were estimated to be 98% viable on the basis of trypan blue dye exclusion. The KC preparations were judged to be 90 to 95% pure after peroxidase staining. Thymocyte Proliferation Assay IL-1 activity in culture supernatants was assayed by the enhancement of the thymocyte proliferation activity as described by Vacheron et al. ...

N-Acetylcysteine prevents baker’s-yeast-induced inflammation and fever

“…In line with this view, a number of studies have shown that S. cerevisiae [32,39] and constituents of its cell wall, such as mannans, cause fever that is accompanied by a putative increase in the plasma levels of TNF-a [15,40], IL-1b and interferon-c [40]. These data are corroborated by the findings of Okawa et al [41], who have shown that mannans increase IL-1b production in vitro, and of Rayhane et al [42] who have reported that the systemic administration of Cryptococcus neoformans does not increase TNF-a levels in murine brain. However, to our knowledge, no study has addressed whether the systemic administration of S. cerevisiae (or its derived mannans) increases IL-1b or TNF-a levels in the hypothalamus, a key cerebral structure for thermoregulation.…”

Hepatic-Targeted Gene Delivery Using Cationic Mannan Vehicle

“…KC and sinusoidal endothelial cells (SEC) are equipped with mannose receptors (MRs), which are important for the recognition of foreign yeast that has mannan in the cell wall. 23 and play an important role in immune-mediated liver diseases such as liver inflammation and fibrosis. 24 Thus, the design of MR-specific carriers to deliver anti-inflammatory or antifibrotic compounds to these cells has great potential for therapy.…”

“…KC and sinusoidal endothelial cells (SEC) are equipped with mannose receptors (MRs), which are important for the recognition of foreign yeast that has mannan in the cell wall . Both cell types are endowed with a high phagocytotic capacity and are part of the reticuloendothelial system (RES) and play an important role in immune-mediated liver diseases such as liver inflammation and fibrosis .…”