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INFLAMMATION AND IMMUNOPHARMACOLOGY

Oral Delivery and Gastrointestinal Absorption of Soluble Glucans Stimulate Increased Resistance to Infectious Challenge

Departments of Pharmacology (P.J.R., B.E.L., D.L.W.), Surgery (E.L.A., T.O.-S., A.J.G., M.P.G., L.A.B., D.L.W.), Obstetrics and Gynecology (P.J.R., K.F.B., W.K.D.), and Biometry and Medical Computing (J.H.K.), College of Medicine, East Tennessee State University, Johnson City, Tennessee; Department of Chemistry (H.E.E.), Tulane University, New Orleans, Louisiana; and Sir William Dunn School of Pathology (G.D.B., S.G.), University of Oxford, Oxford, United Kingdom

Glucans are immunomodulatory carbohydrates found in the cell walls of fungi and certain bacteria. We examined the pharmacokinetics of three water-soluble glucans (glucan phosphate, laminarin, and scleroglucan) after oral administration of 1 mg/kg doses in rats. Maximum plasma concentrations for glucan phosphate occurred at 4 h. In contrast, laminarin and scleroglucan showed two plasma peaks between 0.5 and 12 h. At 24 h, 27 ± 3% of the glucan phosphate and 20 ± 7% of the laminarin remained in the serum. Scleroglucan was rapidly absorbed and eliminated. The liver did not significantly contribute to the clearance of plasma glucan. Biological effects were further studied in mice. Following oral administration of 1 mg, glucans were bound and internalized by intestinal epithelial cells and gut-associated lymphoid tissue (GALT) cells. Internalization of glucan by intestinal epithelial cells was not Dectin-dependent. GALT expression of Dectin-1 and toll-like receptor (TLR) 2, but not TLR4, increased following oral administration of glucan. Oral glucan increased systemic levels of interleukin (IL)-12 (151 ± 15%) in mice. Oral glucan administration also increased survival in mice challenged with Staphylococcus aureus or Candida albicans. These data demonstrate that orally administered water-soluble glucans translocate from the gastrointestinal (GI) tract into the systemic circulation. The glucans are bound by GI epithelial and GALT cells, and they modulate the expression of pattern recognition receptors in the GALT, increase IL-12 expression, and induce protection against infectious challenge.

Address correspondence to: Dr. Peter J. Rice, Department of Pharmacology, East Tennessee State University, P.O. Box 70577, Johnson City, TN 37614. E-mail: rice{at}etsu.edu

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