Immunopharmacology of glucan: a broad spectrum enhancer of host defense mechanisms

Abstract

Department of Physiology, Tulane Umverstty School of Medtcme, New Orleans, LA 70112. USA. An extensive variety of humoral and cellu- lar mechanisms exist to modulate host defense resources in order to maintain the purity and sterility of the internal environ- ment and thus contribute to the well-being of the host. Pharmacological control over these complex and inter-related mechan- isms, a long desired goal, is rapidly approaching reality. As Math6 and Olsson 1 stated in their report in 1979, we have moved from the Middle Ages to the Renais- sance in the development of immunophar- macological agents. It appears that, with the development of muramyl dipeptides and glucan derivatives, we have now rapidly moved from this 'Renaissance' to the emerging Age of Biotechnology. In an environment where drugs are rather specifically designed to mediate a principal pharmacological activity, immunophar- macological agents have the potential to exert what might be considered broad spec- trum activity against a wide variety of dis- ease processes, which have as their origin 'no;~-~c f' or 'altered-self entities. Immun~,~harmacological agents which in- fluence very fundamental host defense sys- tems of the body can regulate the number, funcuonal activity, and interaction of macrophages, T and B lymphocytes, leukocytes and natural killer (NK) cells, as well as their humoral and secretory com- ponents. They therefore possess the potential for non-specifically modifying an extensive array of bacterial, viral, fungal and parasitic infections, as well as neoplastic states. This is a brief review of a unique poly- glucose preparation, glucan, which has been developed by our laboratory to enhance host defense mechanisms in a manner bene- ficial to the continued well-being of the host. This report denotes the immunophar- macological activity of glucan, a /3- 1,3-polyglucose, with accent on its ability to modify a variety of infectious diseases in experimental animals and to function as an adjuvant in vaccine development. The role of glucan in the area of comparative immunopharmacology and developmental therapeutics is also considered. The exten- sive literature on the influence of glucan on experimental clinical neoplasia will not be considered because of space limitations. Except where indicated, the term glucan will denote a particulate glucan preparation isolated from Saccharomyces cerevisiae, which we have now designated glucan-P to distinguish it from other soluble glucans currently under development in our labora- tory, designated glucan-S or glucan -C. Pharmacological activities of glucan-P The i.v. administration of glucan to a variety of experimental animals has been universally demonstrated to result in a marked increase in phagocytic and pro- liferative activity of the reticuloendothelial system (RES) z-5. In association with the proliferative response of the macrophage system, large populations of macrophage elements appear in such organs as liver and spleen resulting in hepatosplenomegaly and granuloma formation. These tissue reac- tions are only observed with glucan-P and not with our new soluble glucans. When glucan is no longer administered, the organs revert back, over a 30-60 day period, to their original weight and normal microscopic structure. Glucan, therefore, allows one to control the functional and pro- liferative activity of the RES. Deimann and FahimP observed that glu- can induced a dose-dependent accumula- tion of macrophages in the liver. By scan- ning electron microscopy, as well as histochemistry, the derivation of Kupffer cells, which are present in massive numbers in the livers of glucan-treated animals, was judged to arise mainly from bone marrow and, to a minor extent, from self-replication in situ. Glucan has been demonstrated, on the basis of electron microscopic observations, to localize exclusively in macrophages of