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Cytokine synthesis in human peripheral blood mononuclear cells after oral administration of polyenzyme preparations

1Desser L., 1Rehberger A., 1Kokron E., 2Paukovits W.

1Institute of Experimental and Applied Oncology

2Institute for Tumor Biology-cancer Research, University of Vienna, Austria

Oncology 1993, 50, pp. 403-407

SO 77 (2-04-1)

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Abstract

Pharmaceutical preparations containing mixtures of various proteolytic and nonproteolytic enzymes have been suggested for use in the treatment of malignant diseases. However, the mode of action of such preparations was not clear. We have shown before that intact bromelain, papain or amylase, which are components of a commercial polyenzyme preparation, induce cytokine production in peripheral blood mononuclear cells in vitro. IFN-a and IFN-g which had no effect alone, synergistically increased TNF production when applied together with the enzymes. Here we show that trypsin alone had only a small inducing effect. The tryptic but not the autolytic fragments of papain and bromelain have a higher (10- to 40-fold) inducing capacity for TNF production than the untreated enzyme. Additionally we demonstrate that after ingestion of milligram doses of the polyenzyme preparation (as recommended for clinical use), PBMNC of healthy donors acquire the ability to produce TNF-a, IL-1b and IL-6 when incubated ex vivo with IFN-g. Our results indicate that the biological effects observed after oral administration of polyenzyme preparations are realted to their ability to induce cytokine production. This may explain the antitumor effects of such enzymes. Our results also suggest that polyenzyme preparations may have a stronger immunomodulary effect when used in combination with IFN-g.

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