IL-10 mediates sigma 1 receptor-dependent suppression of antitumor immunity

J Immunol. 2003 Apr 1;170(7):3585-91. doi: 10.4049/jimmunol.170.7.3585.

Abstract

Sigma receptors are unique endoplasmic reticulum proteins that mediate signaling for a variety of drugs. We determined the effect of sigma(1) receptor agonists on immune responses in a syngeneic lung cancer model. Sigma(1) receptor agonists, including cocaine, up-regulated splenocyte IL-10 mRNA and protein production in vitro in a sigma receptor-dependent, pertussis toxin-sensitive manner. In vivo, sigma(1) receptor agonists promoted tumor growth and induced IL-10 at the tumor site. Increased tumor growth was prevented by administration of specific Abs to IL-10 or by administration of specific sigma(1) receptor antagonists. We report that sigma(1) receptor ligands, including cocaine, augment tumor growth through an IL-10 dependent mechanism.

Publication types

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

MeSH terms

  • Adenocarcinoma, Bronchiolo-Alveolar / chemically induced
  • Adenocarcinoma, Bronchiolo-Alveolar / immunology*
  • Adenocarcinoma, Bronchiolo-Alveolar / pathology*
  • Adenocarcinoma, Bronchiolo-Alveolar / prevention & control
  • Adjuvants, Immunologic / agonists
  • Adjuvants, Immunologic / metabolism
  • Adjuvants, Immunologic / physiology*
  • Adoptive Transfer
  • Animals
  • Antibodies, Monoclonal / administration & dosage
  • Cell Division / drug effects
  • Cell Division / immunology
  • Cocaine / administration & dosage
  • Cocaine / metabolism
  • Cytokines / biosynthesis
  • Down-Regulation / drug effects
  • Down-Regulation / immunology
  • Growth Inhibitors / administration & dosage
  • Immunocompetence / drug effects
  • Injections, Intraperitoneal
  • Injections, Subcutaneous
  • Interferon-gamma / antagonists & inhibitors
  • Interferon-gamma / metabolism
  • Interleukin-10 / biosynthesis
  • Interleukin-10 / immunology
  • Interleukin-10 / physiology*
  • Lung Neoplasms / chemically induced
  • Lung Neoplasms / immunology*
  • Lung Neoplasms / pathology*
  • Lung Neoplasms / prevention & control
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Morpholines / administration & dosage
  • Morpholines / metabolism
  • Neoplasm Transplantation
  • Receptors, sigma / agonists
  • Receptors, sigma / antagonists & inhibitors
  • Receptors, sigma / metabolism
  • Receptors, sigma / physiology*
  • Sigma-1 Receptor
  • Spleen / cytology
  • Spleen / transplantation
  • Tumor Cells, Cultured
  • Up-Regulation / drug effects
  • Up-Regulation / immunology

Substances

  • Adjuvants, Immunologic
  • Antibodies, Monoclonal
  • Cytokines
  • Growth Inhibitors
  • Morpholines
  • Receptors, sigma
  • Interleukin-10
  • 2-(4-morpholino)ethyl-1-phenylcyclohexane-1-carboxylate
  • Interferon-gamma
  • Cocaine