Abstract

Abstract In spite of the use of modern techniques, infection continues to be a leading cause of death in patients subjected to severe trauma and surgical wounds. Previous studies have shown that AHCC, a natural compound, increases survival and prolongs the time to death in a murine model of surgical wound infection. This model simulates some of the conditions that occur after trauma or surgical procedures including systemic infection and food deprivation. To better understand the mechanisms involved in this model, food-deprived mice receiving either AHCC or the excipient were infected with sub-lethal doses of Klebsiella pneumoniae. Organ bacterial load, plasma levels of cytokines, and differential white blood cell counts were determined at different time points after infection. In contrast to control mice, which did not clear bacteria from organs, mice receiving AHCC had significantly reduced numbers of bacteria at day 5 and cleared bacteria entirely from the system at day 6. Levels of IL-12, TNF-α, and IL-6 peaked earlier in this group (day 3) compared with controls (day 5). AHCC also induced a significant increase of numbers of macrophages at day 2 and lymphocytes at day 3. Additional studies indicated that AHCC improved the function of peritoneal cells as measured by nitric oxide production and spleen cell proliferation affected by food deprivation in this model. Taken together, these results suggest that AHCC protects mice restoring the immune system and promoting effective clearance of bacteria and, consequently, a rapid recovery. Funded in part by a grant from the Amino Up Chemical Company, Sapporo, Japan.

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