Beta-glucan is a class of long-chain glucose polymers in beta-(1,3)(1,6) linkage. Beta-glucans are found in the cell wall of fungi, as well as in mushrooms, algae, higher plants, and some bacteria but are not found in mammalian cells and are considered a pathogen-associated molecular pattern (PAMP). Beta-glucans have been shown to have several immunological effects and can stimulate cells of the innate immune system. Priming immune cell function can be of clinical benefit in theory, however, it often results in the overproduction of pro-inflammatory cytokines that may have detrimental consequences to the patient. The soluble, highly purified beta-glucan PGG glucan, which was prepared from Saccharomyces cerevisiae, has been shown to prime antimicrobial functions, including increasing the oxidative burst response, microbicidal activity, and the chemotaxis of leukocytes, without stimulating the production of pro-inflammatory cytokines. Previous in vitro studies were conducted to determine whether this absence of cytokine production is due to a suppressor mechanism. These studies have shown that beta-glucan pretreatment results in attenuation of LPS-induced TNF message, diminishment of LPS-induced TNF protein production, and attenuation of LPS- induced NF- kappa B mediated transcription. Beta-glucan pretreatment was also shown to attenuate LPS- induced serum TNF production in vivo . The prophylactic effects of beta-glucan have been evaluated in preclinical and clinical trials, however, it is unknown if PGG-beta-glucan can be beneficial when given to a patient or an experimental animal that is already infected. Studies described in this proposal are designed to investigate the effects of beta-glucan in septic mice.
The specific aims are:1)To determine the effects of PGG-beta-glucan on the host response of mice to polymicrobial sepsis using treatment protocols that includes prophylactic administration, 2) To determine the effects of PGG-beta-glucan on the mortality of mice to polymicrobial sepsis using treatment protocols that administers PGG-beta-glucan to mice only after the onset of infection. The potential development of beta-glucan as a therapeutic agent with negligible side effects could aid immunocompromised patients, including those undergoing chemotherapy and those with uncontrolled inflammation.
| Newsome, Courtni T; Flores, Estefany; Ayala, Alfred et al. (2011) Improved antimicrobial host defense in mice following poly-(1,6)-?-D-glucopyranosyl-(1,3)-?-D-glucopyranose glucan treatment by a gender-dependent immune mechanism. Clin Vaccine Immunol 18:2043-9 |
