The immunomodulator AS-101 inhibits IL-10 release and augments TNFα and IL-1α release by mouse and human mononuclear phagocytes

Gideon Strassmann, Taku Kambayashi, Chaim O. Jacob, Devora Sredni

Research output: Contribution to journalArticlepeer-review

37 Scopus citations

Abstract

AS-101 is a tellurium-based compound with known immunomodulating properties. The ability of AS-101 to potentiate the effects of chemotherapeutic drugs and augment cytokine production in vivo has led to clinical trials on AS-101 which are currently being carried out in cancer patients. In the present study we show that AS-101 selectively augments the release of TNFα and IL-1α and inhibits the release of IL-10 by lipopolysaccharide (LPS)-stimulated mouse peritoneal macrophages and human monocytes. It does not significantly affect the release of IL-6 or leukemia inhibitory factor (LIF). By itself AS-101 does not induce the release of any of these cytokines. Analysis of IL-10 and TNFα RNA levels using semiquantitative PCR reveals that AS-101 blocks the transcription of IL-10 mRNA, but does not significantly affect TNFα mRNA. Although both AS-101 and interferon (IFN)-γ inhibit IL-10, AS-101, unlike IFN-γ, does not prime macrophages for LPS-induced nitric oxide release and does not appear to significantly affect monocyte HLA-DR expression. Our data suggest that AS-101 is a partial IFN-γ agonist and may explain the shift toward the release of Th-1 type cytokines observed in AS-101-treated patients.

Original languageEnglish
Pages (from-to)180-185
Number of pages6
JournalCellular Immunology
Volume176
Issue number2
DOIs
StatePublished - 15 Mar 1997

Bibliographical note

Funding Information:
This work was partly supported by the Milton and Lois Shiffman NIH CAIR Institute/Bar Ilan University Research Program.

Funding

This work was partly supported by the Milton and Lois Shiffman NIH CAIR Institute/Bar Ilan University Research Program.

FundersFunder number
Milton and Lois Shiffman NIH

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