STUDIES ON OPTIMAL DOSE AND ADMINISTRATION SCHEDULE OF A HEMATOPOIETIC STIMULATORY BETA-(1,4)-LINKED MANNAN

Several complex carbohydrates have been found to significantly stimula te hematopoiesis. CARN 750, a polydispersed beta-(1,4)-linked acetylat ed mannan isolated from the Aloe vera plant, has been shown to have ac tivity in wound repair, to function as a antineoplastic, and to activa te macrophages. We report, herein, the hematoaugmenting properties of CARN 750 and its optimal dose and timing of administration in an anima l model of irradiation-induced myelosuppression. We observed that subc utaneous injections of 1 mg/animal of CARN 750 had equal or greater st imulatory activity for white blood cell (WBC) counts and spleen cellul arity as well as on the absolute numbers of neutrophils, lymphocytes, monocytes and platelets than did higher or lower doses of CARN 750 or an optimal dose of granulocyte-colony stimulating factor (G-CSF). Hema topoietic progenitors, measured as interleukin-3-supported colony form ing units-culture (CFU-C) and high proliferative potential colony-form ing cells (HPP-CFC) assays, were similarly increased by CARN 750 in th e spleen but not in the bone marrow. The frequency of splenic HPP-CFCs and absolute number of splenic HPP-CFCs and CFU-Cs were optimally inc reased by 1 mg/animal of CARN 750. In contrast, bone marrow cellularit y, frequency and absolute number of HPP-CFCs and CFU;Cs had as a dosag e optimum 2 mg/animal of CARN 750. These parameters were similarly inc reased by G-CSF. In studies to determine the optimal protocol for the administration of CARN 750 we found that the hematopoietic activity of CARN 750 increased with the frequency of administration. The greatest activity in myelosuppressed mice was observed for all hematopoietic p arameters except the platelet number in mice receiving daily administr ation of 1 mg/animal of CARN 750 with activity equal to or greater tha n G-CSF.