Treatments for the activating macrophages that reduces surgical stress and postoperative mortalities from bacterial infections and tumor metastases.

BACKGROUND: Some of the mortalities caused by infectious diseases and/or distant metastases following surgery are thought to be due to immunological suppression. For this reason, techniques that reduce immunological suppression following surgery may reduce mortalities and/or incidences of micrometastases in distant organs. MATERIALS AND METHODS: Mice were anesthetized and their peritoneal cavities were opened for 30 min. Immunological suppression was estimated by the presence of tumor necrosis factor-a (TNF) after injection with OK-432 (dead bacterial bodies). The mice were administered with either Staphylococcus aureus or cancer cells of Meth A fibrosarcoma. Survival times and lung metastastic foci were then observed at 3 weeks. Results were compared for mice with or without treatment by OK432 or TNF prior to surgery. RESULTS: While significant suppression of TNF production was observed after laparotomy, administration of a macrophage-activating agent (TNF or OK-432) 3 h prior to laparotomy prevented immune suppression after the laparotomy. Laparotomy increased mortalities from bacterial infections and promoted the number of lung metastases. By contrast, administration of TNF or OK-432 3 h prior to the laparotomy decreased mortalities and metastases after the laparotomy. CONCLUSION: These results suggest that appropriate activation of macrophages prior to surgery is a method to reduce some of the detrimental effects caused by surgical operations.

Identification and characterization of lipopolysaccharide in acetic acid bacteria.

BACKGROUND: Lipopolysaccharide (LPS), a major component of the cell walls of Gram-negative bacteria, was one of the main components of Coley's vaccine and is known to have strong adjuvanticity. Though it is known that LPS exists in the digestive tract of organisms, the biological significance for the organism has not been clarified. In this study, the correlation between the structure and function of LPS was determined using acetic acid bacteria. These are Gram-negative bacteria consumed in human diets. MATERIALS AND METHODS: Extracts were obtained from a strain of acetic acid bacteria which is used for producing vinegar. Determination of the LPS neutralizing activity was carried out by the Limulus test. Tumor necrosis factor (TNF) and nitric oxide (NO) production were then observed after the addition of the extracts to murine monocyte macrophages (RAW264. 7), with or without Polymyxin B. TNF production in peritoneal macrophages derived from LPS-low responsive mice (C3H/HeJ) was studied after the addition of extracts. RESULTS: The extracts were shown to be positive only in LPS-specific Limulus test and were negative in the (1,3)-beta-D-glucan-specific Limulus test. Both extracts induced NO and TNF production in RAW264. 7 cells, but this was inhibited by the presence of Polymyxin B. TNF production was inhibited in peritoneal macrophages from LPS low-responsive mice (C3H/HeJ). CONCLUSION: LPS with macrophage-activating activity is present in acetic acid bacteria, routinely consumed by humans.

Applications of lipopolysaccharide derived from Pantoea agglomerans (IP-PA1) for health care based on macrophage network theory.

Innate immunity is a universal prophylactic system which all multi-cellular animals possess. Macrophages are the cells that play the central role in the innate immune system. In 1991, we discovered a substance in a water extract of wheat flour that activated macrophages after oral or intradermal administration. The active substance was lipopolysaccharide (LPS), which is derived from the cell walls of Pantoea agglomerans, gram-negative bacteria that grows symbiotically with wheat. We named the substance IP-PA1 (immuno potentiator from P. agglomerans, former name: LPSp). The IP-PA1 is considered to be useful in various fields such as health food (to prevent and improve metabolic syndromes), skincare products (to maintain healthy skin, to improve atopic dermatitis, and to resist aging), and as active ingredients in feeds for stockbreeding and aquaculture (to act as a defense against infection). In this manuscript, we discuss the significance of activation of macrophages through oral or intradermal administration, the discovery of IP-PA1 as a macrophage-activating substance, the chemical structure of IP-PA1, the use of IP-PA1 to improve various disorders, the mechanism of action, and the possibility of application of IP-PA1 to various fields.