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Supplement: Immunonutrition: Enhancing Tumoricidal Cell Activity

Are Botanical Glucans Effective in Enhancing Tumoricidal Cell Activity?¹

Department of Pediatrics, The Weill Medical College of Cornell University, New York, NY

²To whom correspondence should be addressed. E-mail: scrundle{at}med.cornell.edu.

KEY WORDS: • Maitake mushroom • Grifola frondosa • bone marrow cell • hematopoiesis

Studies of nutrient immune interactions have shown that protein calorie malnutrition and micronutrient deficiency impair immune development and immune response especially in critical phases of life. More recently, important data on the role of fatty acids in immune responses has emerged. The question of how or when dietary intervention might augment immune response or reduce any specific disease expression remains open. A fundamental issue is how to design an experimental approach that reveals key relationships so that we can examine relevant change. Current studies on how the adaptive immune response is regulated by the innate immune response in the microenvironment may be particularly useful, because this may be the level at which nutrient action occurs.

One common pathway for the action of certain carbohydrates isolated from mushroom, barley, and other sources, including various microbes, may involve effects on cellular differentiation and trafficking from bone marrow and other hematopoietic sites. We have been working with a purified extract from the Maitake mushroom (Grifola frondosa) with the objective of studying the effects of MD³ fraction as an oral adjuvant in cancer patients. Previous studies in the mouse have used intraperitoneal or intravenous injection to assess the effects of Maitake mushroom on the growth of implanted tumors and various adjuvant-like effects have been observed. However, dose–response relationships were elusive. Because some other beta-glucans appear to promote mobilization of hematopoietic stem cells, we used a colony-forming assay (CFU-GM) to study the effects of MD-fraction (MDF) on hematopoietic stem cells. We found a dose–response effect on mouse bone marrow cell (BMC) hematopoiesis in vitro. The data showed that the addition of MDF significantly enhanced the development of CFU-GM. The mechanism of action included significant increase of nonadherent BMC viability even in the presence of doxorubicin (DOX). MDF promoted BMC viability and protected CFU-GM from DOX-induced toxicity. In addition, MDF treatment promoted the recovery of CFU-GM colony formation after BMCs were pretreated with DOX. We have extended these observations to human cord, and peripheral blood and to cell lines and observed that this botanical activates a selective pattern of response that may model the effects of other dietary elements on immune response.

FOOTNOTES

¹ Published in a supplement to The Journal of Nutrition. Presented during a workshop entitled: "Immunonutrition: Enhancing Tumoricidal Cell Activity," held in Bethesda, MD, March 23, 2005. This workshop was sponsored by the Division of Cancer Prevention, NCI, NIH, DHHS. Guest editors for the supplement publication were Susan S. Percival, John A. Milner, and Christopher A. Jolly. Guest Editor Disclosure: Susan S. Percival: no relationships to disclose; John A. Milner: no relationships to disclose; Christopher A. Jolly: received reimbursement for travel expenses from NCI.

³ Abbreviations used: BMC, bone marrow cell; CFU-GM, colony-forming assay; DOX, doxorubicin; MD; MDF, MD-fraction.

LITERATURE CITED

1. Rivlin RS, Cunningham-Rundles S. Cancer Prevention. Walker WA Watkins JB Duggan C eds. Cancer Prevention. Nutrition in Pediatrics: basic science and clinical application. 3rd ed. :699-708 BC Decker Hamilton, Ontario.

2. Cunningham-Rundles S, McNeeley DF. Malnutrition and host defenses. Walker WA Watkins JB Duggan C eds. Malnutrition and host defenses. Nutrition in Pediatrics: basic science and clinical application. 3rd ed. :367-385 London: BC Decker Hamilton, Ontario.

3. Cunningham-Rundles S. Assessment of human immune response. Hughes DA Darlington JG Bendich A eds. Assessment of human immune response. Diet and human immune function. :17-34 Humana Press Totowa, NJ.

4. Lin H, She Y-H, Cassileth BR, Sirotnak F, Cunningham-Rundles S. Maitake beta-glucan MD-fraction enhances bone marrow colony formation and reduces doxorubicin toxicity in vitro. Int Immunopharmacol. 2004;4:91-99.[Medline]

5. Cunningham-Rundles S. The effect of aging on mucosal host defense. J Nutr Health Aging. 2004;8:20-25.[Medline]

6. Cunningham-Rundles S, McNeely D, Ananworanich, JM. Immune Response in Malnutrition. Stiehm ER Ochs HD Winkelstein JA eds. Immune Response in Malnutrition. Immunologic disorders in infants and children. 5th ed. :761-784 Elsevier Saunders.

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