Oncostatin M: development of a pleiotropic cytokine

Toxicol Pathol. 1999 Mar-Apr;27(2):151-5. doi: 10.1177/019262339902700201.

Abstract

Oncostatin M (OM) is a member of the interleukin-6 (IL-6) cytokine subfamily. The binding of OM to its receptor initiates signal transduction through JAK-signal transducers and activators of transcription (STAT) pathways and activates transcription activators through mitogen-activated protein (MAP) kinases. Results of in vitro assays documented that OM modulates cytokine expression and alters the production of proteases that down-regulate inflammation. Administration of OM to lipopolysaccharide (LPS)-challenged mice lowered serum tumor necrosis factor-alpha (TNF-alpha) levels and decreased the lethal effects of LPS administration. OM also reduced inflammation in animal models of human disease, including inflammatory bowel disease, antibody-induced arthritis, and experimental autoimmune encephalomyelitis. Preclinical safety studies have been conducted in the mouse and monkey. Mice were administered OM (subcutaneously) at 72, 360, or 1,560 micrograms/kg/day in a 2-wk toxicity study. Decreased body weights occurred at 1,560 micrograms/kg. Drug-related changes at 360 and 1,560 micrograms/kg consisted of dermal irritation at the injection site, leukopenia, and thymic lymphoid depletion; all changes were reversible following a 2-wk recovery period. In a 2-wk subcutaneous study in monkeys, OM was administered at 1, 5, 15, 45, or 150 micrograms/kg/day. At all doses there was reversible, transient inappetence and dermal irritation at the injection site. Drug-related changes at 5, 15, 45, and 150 micrograms/kg consisted of reversible elevations in both serum amyloid A and IL-6, and reversible thymic lymphoid depletion. Transient increases in body temperature occurred at 15, 45, and 150 micrograms/kg. The observed spectrum of immunomodulatory effects suggests that OM may have therapeutic utility in treating chronic inflammatory diseases.

Publication types

  • Congress
  • Review

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / pharmacology
  • Anti-Inflammatory Agents / therapeutic use
  • Antineoplastic Agents / pharmacology*
  • Antineoplastic Agents / therapeutic use
  • Cytokines / drug effects
  • Cytokines / metabolism
  • Disease Models, Animal
  • Humans
  • Inflammation / drug therapy
  • Inflammation / metabolism
  • Oncostatin M
  • Peptides / pharmacology*
  • Peptides / therapeutic use

Substances

  • Anti-Inflammatory Agents
  • Antineoplastic Agents
  • Cytokines
  • OSM protein, human
  • Osm protein, mouse
  • Peptides
  • Oncostatin M