A role for tumor necrosis factor in poly(I:C)-induced hemorrhagic necrosis and T-cell-dependent regression of a murine sarcoma

J Interferon Res. 1991 Dec;11(6):333-40. doi: 10.1089/jir.1991.11.333.

Abstract

It was found that intravenous injection of the synthetic double-stranded ribonucleic acid, polyinosinic-polycytidylic acid [poly(I:C)], which is a well-studied interferon (IFN)-inducing agent, can result in extensive hemorrhagic necrosis of the center of an established murine sarcoma and in subsequent complete regression of the surviving rim of the tumor. The poly(I:C)-induced intratumor hemorrhagic reaction was associated with production of appreciable quantities of tumor necrosis factor (TNF) by the host. Neutralization of TNF by treatment with anti-rTNF immunoglobulin G (IgG) caused substantial inhibition of hemorrhagic necrosis and prevented tumor regression from proceeding. Tumor regression was prevented in all mice by depleting them of CD8+ T cells 1 day before poly(I:C) was given. Taken as a whole, the results indicate that the antitumor action of poly(I:C), like that of endotoxin, is based on its capacity to induce the host to make enough TNF to cause a hemorrhagic reaction extensive enough to reduce the tumor burden to a size capable of being dealt with by an underlying host antitumor immune response.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Endotoxins / administration & dosage
  • Female
  • Hemorrhage / pathology*
  • Immunoglobulin G / immunology
  • Injections, Intravenous
  • Mice
  • Mice, Inbred A
  • Mice, Inbred C57BL
  • Necrosis
  • Poly I-C / administration & dosage
  • Poly I-C / pharmacology*
  • Recombinant Proteins
  • Remission Induction
  • Salmonella enteritidis
  • Sarcoma, Experimental / immunology
  • Sarcoma, Experimental / pathology
  • Sarcoma, Experimental / therapy*
  • T-Lymphocytes / immunology*
  • T-Lymphocytes, Regulatory / immunology
  • Tumor Necrosis Factor-alpha / biosynthesis*
  • Tumor Necrosis Factor-alpha / immunology

Substances

  • Endotoxins
  • Immunoglobulin G
  • Recombinant Proteins
  • Tumor Necrosis Factor-alpha
  • Poly I-C