Abstract

1.A functional description of immunity

1.1. Innate immunity: The “standing army” of infection defense

1.2. Epithelial surface defense

1.3. The mesenchymal defense

1.4. Innate immune cells monitor the microbial environment

1.5. The specific immune system

2.Activation of innate immunity by microbial products

2.1. Immune-stimulants and immune-modulators

2.2. Immune modulating beta-1,3/1,6-glucans and medical indications

2.3. Use of beta-1,3/1,6-glucans in domestic animals

3.The history of beta-1,3/1,6-glucans

3.1. Beta-1,3/1,6-glucans in Oriental medicine

3.2. Zymosan and beta-1,3/1,6-glucan in baker’s yeast

4.Chemistry, properties and manufacture of glucans and beta-1,3/1,6-glucans

4.1. What is a glucan and what determines its immune stimulating
 property?

4.2. Brewer’s yeast

4.3. Oat and barley glucans

4.4. Micro-particulate beta-1,3/1,6-glucan from baker’s yeast

4.5. Soluble beta-1,3/1,6-glucans from baker’s yeast

5.Mode of action and biological effects

5.1. Recognition of beta-1,3/1,6-glucans by phagocytic cells

5.2. Induction of IFN-gamma in gut lymphocytes by microparticulate beta-1,3/1,6-glucan

5.3. Effect on mucous: Induction of antigen specific Tcells in spleen

5.4. Higher milk IgG

6.Safety

6.1. General

6.2. Experience from practical use

6.3. No immunogenicity

6.4. Formal safety studies: Basis for clinical trials

6.4.1. Micro-particulate yeast beta-1,3/1,6-glucan

6.4.2. Soluble native beta-1,3/1,6-glucan from yeast

7.Selected pre-clinical “proof-of-concept” studies

7.1. Effects of postirradiation carboxymethylglucan administration in mice (Hofer et al. 1995).

7.2. Isolation, physicochemical characterization and preclinical efficacy evaluation of soluble scleroglucan (Pretus et al. 1991).

7.3. Development, physicochemical characterization and preclinical efficacy, evaluation of a water-soluble glucan sulphate derived from Saccharomyces cerevisiae (Williams et al. 1992).

7.4. Tumor regression after treatment with aminated beta 1-3D polyglucose is initiated by circulatory failure (Seljelid 1989).

7.5. Soluble yeast beta-1,3/1,6-glucan in cosmetic formulations (patents WO 0054734, WO 0054742 and WO 0054739)

8.Description of selected clinical trials

8.1. A “proof-of-concept”, double blind, parallel group study comparing the immune modulating and lipid lowering effects of beta-1,3/1,6-glucan (Immutol) with that of placebo (cellulose) in subjects with mild to moderate hypercholesterolemia (Biotec Pharmacon ASA, N-9008 Tromsø, Norway, 2003).

8.2. Randomized phase I/II trial of a macrophage-specific immunomodulator (PGG-Glucan) in high-risk surgical patients (Babineau et al. 1994b)

8.3. A phase II multicenter, double-blind, randomized, placebo-controlled study of three dosages of an immunomodulator (PGG-Glucan) in high-risk surgical patients (Babineau et al. 1994a)

8.4. Effect of PGG-glucan on the rate of serious postoperative infection or death observed after high-risk gastrointestinal operations (Phase III study) (Dellinger et al. 1999)

8.5. Infection prevention in patients with severe multiple trauma with the immunomodulator beta 1-3 polyglucose (glucan) (Felippe et al. 1993).

8.6. Beneficial effect of enhanced macrophage function in the trauma patient (Browder et al. 1990).

8.7. Effectiveness of beta-glucan collagen for treatment of partial-thickness burns in children (Delatte et al. 2001).

9.Skepticism to beta-1,3/1,6-glucan

10.Conclusion

References