The immunomodulator AS-101 inhibits IL-10 release and augments TNF alpha and IL-1 alpha release by mouse and human mononuclear phagocytes.

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 TNF alpha and IL-1 alpha 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 TNF alpha RNA levels using semiquantitative PCR reveals that AS-101 blocks the transcription of IL-10 mRNA, but does not significantly affect TNF alpha mRNA. Although both AS-101 and interferon (IFN)-gamma inhibit IL-10, AS-101, unlike IFN-gamma, 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-gamma agonist and may explain the shift toward the release of Th-1 type cytokines observed in AS-101-treated patients.

• Authors: G Strassmann, T Kambayashi, C O Jacob, D Sredni
• Journal: Cellular immunology (Cell Immunol) Vol. 176 Issue 2 Pg. 180-5 (Mar 15 1997) ISSN: 0008-8749 [Print] Netherlands
• PMID: 9073392 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Adjuvants, Immunologic
• Ethylenes
• HLA-DR Antigens
• Interleukin-1
• Lipopolysaccharides
• RNA, Messenger
• Tumor Necrosis Factor-alpha
• Interleukin-10
• ammonium trichloro(dioxoethylene-O,O'-)tellurate
• Interferon-gamma

Topics

• Adjuvants, Immunologic (pharmacology)
• Animals
• Cells, Cultured
• Ethylenes (pharmacology)
• HLA-DR Antigens (biosynthesis)
• Humans
• Interferon-gamma (pharmacology)
• Interleukin-1 (metabolism)
• Interleukin-10 (antagonists & inhibitors, genetics, metabolism)
• Lipopolysaccharides (pharmacology)
• Macrophages, Peritoneal (drug effects, metabolism)
• Male
• Mice
• Mice, Inbred C57BL
• Monocytes (drug effects, metabolism)
• RNA, Messenger (biosynthesis)
• Tumor Necrosis Factor-alpha (drug effects, genetics, metabolism)