Subtherapeutic Corticosteroids Potentiate the Ability of Interleukin 10 to Prevent Chronic Inflammation in Rats

Gastroenterology. 1998 Oct;115(4):856-65. doi: 10.1016/s0016-5085(98)70257-4.

Abstract

Background & aims: Interleukin (IL)-10, which inhibits macrophages and T-helper lymphocyte type 1 (TH1) lymphocytes, attenuates chronic granulomatous inflammation induced by bacterial cell wall polymers. This study determines whether corticosteroids enhance the protective effects of IL-10 in cultured peripheral blood mononuclear cells (PBMNCs) and in vivo when started before or after the onset of experimental chronic granulomatous inflammation.

Methods: Intestines of Lewis rats were injected intramurally with streptococcal peptidoglycan-polysaccharide (PG-APS) polymers. Daily murine recombinant IL-10 and/or dexamethasone (DEX) therapy was started 12 hours before or at several intervals after PG-APS injection.

Results: IL-10 plus corticosteroids additively inhibited IL-1beta secretion in human PBMNCs but preserved the beneficial IL-1RA/IL-1beta ratio induced by IL-10. IL-10 started before PG-APS injection significantly attenuated intestinal and extraintestinal inflammation, with even more pronounced effects in combination with subtherapeutic doses of DEX. The combination of DEX decreased the effective dose of IL-10 by at least one half. After onset of systemic inflammation using doses effective for prevention, IL-10 monotherapy had nearly no benefit and DEX plus IL-10 was similar to the mild therapeutic effect of DEX alone.

Conclusions: The combination of IL-10 and corticosteroids allows lower doses of both agents in preventing chronic intestinal and systemic inflammation. However, timing of IL-10 administration is a critical variable in regulating inflammation.

Publication types

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

MeSH terms

  • Animals
  • Cells, Cultured
  • Chronic Disease
  • Dexamethasone / administration & dosage
  • Dexamethasone / therapeutic use*
  • Dose-Response Relationship, Drug
  • Drug Synergism
  • Drug Therapy, Combination
  • Enterocolitis / drug therapy
  • Enterocolitis / prevention & control*
  • Female
  • Glucocorticoids / administration & dosage
  • Glucocorticoids / therapeutic use*
  • Humans
  • Inflammation / drug therapy
  • Inflammation / prevention & control*
  • Interleukin-1 / metabolism
  • Interleukin-10 / administration & dosage
  • Interleukin-10 / therapeutic use*
  • Rats
  • Rats, Inbred Lew
  • Receptors, Interleukin-1 / antagonists & inhibitors
  • Recombinant Proteins

Substances

  • Glucocorticoids
  • Interleukin-1
  • Receptors, Interleukin-1
  • Recombinant Proteins
  • Interleukin-10
  • Dexamethasone