Research
Active hexose correlated compound activates immune function to decrease bacterial load in a murine model of intramuscular infection

https://doi.org/10.1016/j.amjsurg.2007.05.045Get rights and content

Abstract

Background

Infection is a serious, costly, and common complication of surgery and constitutes the principal cause of late death in patients undergoing surgery. The objective of this study was to clarify the mechanisms by which active hexose correlated compound (AHCC) increases survival in a murine model of intramuscular infection.

Methods

Food-deprived mice receiving either AHCC or excipient were infected with bacteria. Kinetics of bacterial load, white blood cell counts, cytokine levels, and antibody levels were compared between groups.

Results

AHCC-treated mice had reduced bacterial load at day 5 and cleared bacteria entirely at day 6. Levels of interleukin-12, tumor necrosis factor-α, and interleukin-6 peaked earlier in this group (day 3) compared with controls (day 5). Increased percentages of peripheral lymphocytes and monocytes and decreased numbers of polymorphonuclear cells were detected in the AHCC group.

Conclusions

AHCC appears to induce an early activation of the immune response, leading to an effective clearance of bacteria and rapid recovery.

Section snippets

Bacteria

Klebsiella pneumoniae strain ATCC 43816 was obtained from American Type Culture Collection (Bethesda, MD). Stock cultures of the bacterium were maintained in tryptic soy broth (TSB) medium plus 50% glycerol and stored at −80°C until use.

Animals

Specific pathogen–free female Swiss/Webster mice (9–11 wk, each weighing 21–25 g) were purchased from Harlan Sprague-Dawley Laboratories (Indianapolis, IN). Animals were housed in a quiet, isolated room with controlled temperature, light cycle, and having access

Oral administration of AHCC promotes the clearance of bacteria from blood and organs in food-deprived and K pneumoniae–infected mice

We have shown in previous studies that AHCC increases the survival of mice in a rodent model of intramuscular infection [9]. To assess the role of AHCC on the progress of infection in this model, AHCC-treated and control mice were infected with sublethal doses of K pneumoniae, and the presence of bacteria was determined in blood and organs in successive days after infection. Fig. 1 shows the kinetics of bacterial organ load of food-deprived and infected mice receiving either AHCC or the

Comments

One of the most important aspects in the care of surgical patients continues to be the prevention and diligent control of microbial contamination. Among postoperative complications, infection constitutes the major limiting factor for recovery of patients after surgery or severe trauma [41]. Malnutrition is an important risk factor and has been associated with a higher incidence of postoperative infections [18], [42], [43]. Abstinence from food and drink before and after surgery is a common

Acknowledgments

This work was funded by a grant from the Amino Up Chemical Company (Sapporo, Japan).

The authors thank Hiroshi Nishioka for his comments and critical review of the manuscript.

References (59)

  • T. Belay et al.

    Catecholamines and in vitro growth of pathogenic bacteria: enhancement of growth varies greatly among bacterial species

    Life Sci

    (2003)
  • W. Altemeier

    Sepsis in surgeryPresidential address

    Arch Surg

    (1982)
  • E. Abraham et al.

    Efficacy and safety of monoclonal antibody to human tumor necrosis factor alpha in patients with sepsis syndromeA randomized, controlled, double-blind, multicenter clinical trial. TNF-alpha Mab Sepsis Study Group

    JAMA

    (1995)
  • K. Reinhart et al.

    Randomized placebo-controlled trial of the anti-tumor necrosis factor antibody fragment afelimomab in hyperinflammatory response during severe sepsis: the Ramses study

    Crit Care Med

    (2001)
  • D. Heldricks et al.

    Surgical aspects of infection

  • R. Goris et al.

    Causes of death after blunt trauma

    J Trauma

    (1982)
  • F. Gottrup et al.

    An overview of surgical site infections: aetiology, incidence and risk factors. World Wide Wounds

  • H. Aviles et al.

    Active hexose correlated compound enhances resistance to infection in a mouse model of surgical wound infection

    Surg Infect

    (2006)
  • M. Hershman et al.

    Modulation of Klebsiella pneumoniae infection of mice by interferon-γ

    Clin Exp Immunol

    (1988)
  • H. Polk et al.

    A systematic study of host defense processes in badly injured patients

    Ann Surg

    (1980)
  • M. Rodrick et al.

    Mechanisms of immunosuppression associated with severe nonthermal traumatic injuries in man: production of interleukin 1 and 2

    J Clin Immunol

    (1986)
  • E. Faist et al.

    Alteration of monocyte function following major injury

    Arch Surg

    (1988)
  • E. Pallinger et al.

    Influence of acute stress on the triiodothyronine (T3) and serotonin content of rat’s immune cells

    Acta Physiol Hung

    (2005)
  • P. Duggal et al.

    Effects of leptin administration and feed restriction on thecal leucocytes in the preovulatory rat ovary and the effects of leptin on meiotic maturation, granulosa cell proliferation, steroid hormone and PGE2 release in cultured rat ovarian follicles

    Reproduction

    (2002)
  • R. Galland et al.

    Non-specific stimulation of host defenses against a bacterial challenge in malnourished hosts

    Br J Surg

    (1982)
  • H. Aviles et al.

    Active hexose correlated compound enhances resistance to Klebsiella pneumoniae infection in mice in the hindlimb-unloading model of spaceflight conditions

    J Appl Physiol

    (2003)
  • P. Kidd

    The use of mushrooms glucans and proteoglycans in cancer treatment

    Altern Med Rev

    (2000)
  • N. Kodama et al.

    Administration of a polysaccharide from Grifola frondosa stimulates immune function of normal mice

    J Med Food

    (2004)
  • S. Wang et al.

    Beneficial effects of active hexose correlated compound on immobilization stress in the rat

    Dokkyo J Med Sci

    (2001)
  • Cited by (34)

    • Immunotherapy in clinical canine leishmaniosis: a comparative update

      2019, Research in Veterinary Science
      Citation Excerpt :

      Dietary nucleotides have been widely studied and used to increase lipid metabolism, immune responses as well as the development and repair of tissue growth in human infants (Carver et al., 1991; Navarro et al., 1999) and rodents (Jyonouchi et al., 1996, 1994; Van Buren et al., 1985). Active hexose correlated compounds (AHCC) are alpha-glucan-rich dietary supplements extracted from mushrooms that has been reported to have antioxidant activity and induce improvement of the Th1 immune response associated with increment of NK cells, T cells, B cells and cytokines such as IL-12 and TNF-α in human PBMCs and rodents (Lee et al., 2012; Aviles et al., 2008). A study performed with BALB/c mice investigated the effect of dietary nucleotides on the immune function (Xu et al., 2013) demonstrating that dietary nucleotides could enhance the innate and adaptive immune responses of mice through stimulation of Th cells and cytokines (Xu et al., 2013).

    • Therapeutic effect of Active Hexose-Correlated Compound (AHCC) combined with CpG-ODN (oligodeoxynucleotide) in B16 melanoma murine model

      2015, Cytokine
      Citation Excerpt :

      Active hexose correlated-compound (AHCC) is an extract obtained from L. edodes of Basidiomycetes family that is commercially available in Japan as a supplement for cancer patients who are undergoing chemotherapy. AHCC has been proven to stimulate cytokines (IL-2, IL-6, IL-12 and TNF-α) [7] and boost the immune system as an immunomodulator [8–10]. In addition, supplementation of AHCC showed various positive effects against cancer, such as decreased tumor formation [11] and increased immune response [8,10].

    • Adenosine, a hepato-protective component in active hexose correlated compound: Its identification and iNOS suppression mechanism

      2014, Nitric Oxide - Biology and Chemistry
      Citation Excerpt :

      Functional food, active hexose correlated compound (AHCC), is an extract prepared from cultured mycelium of a Basidiomycetes mushroom. Recent reports have shown that supplementation with AHCC exerts a general positive effect on the immune system, as well as anti-inflammatory and anti-oxidant effects [8–13]. AHCC is a mixture of poly- and oligo-saccharides, amino acids, lipids, minerals, etc., in which oligosaccharides are the major components, comprising approximately 74% of the mixture.

    View all citing articles on Scopus
    View full text