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

Research output: Contribution to journalArticle

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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