Production of IL-1 and IL-1 receptor antagonist and the pathological significance in lipopolysaccharide-induced arthritis in rabbits

A. Matsukawa, S. Ohkawara, T. Maeda, K. Takagi, M. Yoshinaga

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68 Citations (Scopus)

Abstract

Injection of lipopolysaccharide (LPS) into rabbit knee joints provoked leucocyte infiltration and loss of proteoglycan (PG) from the cartilage. We investigated the role of IL-1 and IL-1 receptor antagonist (IL-1Ra) and its significance in the pathogenesis of LPS-arthritis. Production of IL-1β peaked at 6 h (196.7 ± 89.4 pg/joint) after injection of 10 ng of LPS, while IL-1Ra peaked at 9 h (34.5 ± 13.4 ng/joint). The amount of IL-1Ra was 180-200-fold molar excess of IL-1, and a large amount of IL-1Ra was sustained for 1 week. Both IL-1β and IL-1Ra were mainly produced by synovial exudate cells. Arthritis was reproduced by rabbit IL-1β. LPS-induced leucocyte infiltration was inhibited 70-75% by rabbit IL-1Ra. Loss of PG in LPS-arthritis was prevented by IL-1Ra and also by neutrophil elastase inhibitor, and superoxide dismutase. In leucopenic rabbits, injection of LPS induced neither production of IL-1β nor loss of PG. Direct injection of inflammatory exudated cells in leucopenic rabbits reproduced loss of PG, and there was only a partial recovery by IL-1Ra. These results suggest that LPS-initiated IL-1 acts as a key mediator in LPS-arthritis and that endogenous IL-1Ra may suppress a part of IL-1 activity at the site, but its amount was too low for suppression of the produced IL-1. Loss of PG is a sequela of infiltrated leucocytes and leucocyte-derived elastase, and superoxide anion may play a pivotal role in the destruction of cartilage.

Original languageEnglish
Pages (from-to)206-211
Number of pages6
JournalClinical and Experimental Immunology
Volume93
Issue number2
DOIs
Publication statusPublished - 1993
Externally publishedYes

Keywords

  • cytokine production in vivo
  • leucocyte infiltration
  • neutrophil elastase
  • proteoglycan degradation
  • superoxide anion

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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