In vivo synergistic effect of the immunomodulator AS101 and the PKC inducer bryostatin

Y. Kalechman, M. Albeck, B. Sredni

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21 Scopus citations

Abstract

The immunomodulator AS101 has recently been found to have radioprotective properties when injected prior to sublethal and lethal doses of irradiation. In addition, this compound was found to protect mice from hemopoietic damage caused by sublethal doses of cyclophosphamide (CYP) and to increase the rate of survival of mice treated with lethal doses of CYP. AS101 was previously shown to exert a synergistic effect with the PKC-inducer bryostatin in cytokine secretion in vitro. The present studies were designed to evaluate the effects of in vivo combined treatment with AS101 and bryostatin on bone marrow and spleen cellularity and on the number of committed progenitors in the bone marrow at various points of time after their treatment with a sublethal dose of CYP or irradiation. In addition, the combined effect was tested on the survival of mice irradiated with a lethal dose of irradiation. Our data show the presence of synergism which greatly enhances the number of bone marrow and spleen cells 48 hr and 9 days after CYP treatment or irradiation. The combined effect was also demonstrated when bone marrow colony-forming units granulocyte-macrophage (CFU-GM) progenitor cells were evaluated. Moreover, AS101 and bryostatin synergized in their protective effects against lethal damages of irradiation. These results strongly suggest that bryostatin, which lacks tumor-promoting activity, is a particularly good candidate in combination with AS101 for treatment in vivo in counteracting chemotherapy- or radiation-induced hematopoietic suppression or in generally improving the restoration of immune response under conditions involving immune or hemopoietic damage.

Original languageEnglish
Pages (from-to)143-153
Number of pages11
JournalCellular Immunology
Volume143
Issue number1
DOIs
StatePublished - Aug 1992

Bibliographical note

Funding Information:
’ This work was partly supported by the Dorsha Wallman Cancer Chair. 2 Abbreviations used: PKC. protein kinase C; IL-2 interleukin-2; IFN, interferon: CYP. cyclophosphamide: CFU-GM, colony forming unit granulocyte-macrophage.

Funding

’ This work was partly supported by the Dorsha Wallman Cancer Chair. 2 Abbreviations used: PKC. protein kinase C; IL-2 interleukin-2; IFN, interferon: CYP. cyclophosphamide: CFU-GM, colony forming unit granulocyte-macrophage.

FundersFunder number
Dorsha Wallman Cancer Chair

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