Increased polyamines may downregulate interleukin 2 production in rheumatoid arthritis

J Clin Invest. 1989 Apr;83(4):1356-62. doi: 10.1172/JCI114023.

Abstract

Polyamines downregulate immune reactivity. RA is associated with decreased IL 2 production. In this study, we present evidence to suggest that excessive polyamines can contribute to the IL 2 deficiency in RA. Blocking polyamine production with inhibitors of ornithine decarboxylase results in increased IL 2 production by RA PBMC. Moreover, polyamine oxidase (PAO) inhibitors and catalase also increase IL 2 production by RA PBMC. This effect of PAO inhibition is monocyte mediated. After 3 d in culture, RA PBMC produce three times more IL 2 than do normal PBMC. This rise is prevented by exogenous spermidine but only in the presence of monocytes. The concentration of polyamines in RA PBMC and synovial fluid MNC is 2-20-fold higher than in normal cells. Thus, polyamines and their oxidation products downregulate IL 2 production by RA PBMC and may account for the decreased T cell effector function seen in this disease.

Publication types

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

MeSH terms

  • Adult
  • Aged
  • Arthritis, Rheumatoid / immunology
  • Arthritis, Rheumatoid / metabolism*
  • Biogenic Polyamines / biosynthesis
  • Biogenic Polyamines / metabolism
  • Biogenic Polyamines / physiology*
  • Cell Separation
  • Cells, Cultured
  • Female
  • Humans
  • Hydrogen Peroxide / physiology
  • Interleukin-2 / biosynthesis*
  • Interphase / drug effects
  • Male
  • Middle Aged
  • Monocytes / physiology
  • Oxidoreductases Acting on CH-NH Group Donors / antagonists & inhibitors
  • Prostaglandins / physiology
  • Spermidine / pharmacology
  • T-Lymphocytes / physiology

Substances

  • Biogenic Polyamines
  • Interleukin-2
  • Prostaglandins
  • Hydrogen Peroxide
  • Oxidoreductases Acting on CH-NH Group Donors
  • polyamine oxidase
  • Spermidine