Open AccessProduction of IL‐1 and IL‐1 receptor antagonist and the pathological significance in lipopolysaccharide‐induced arthritis in rabbits
Author(s) -
MATSUKAWA A.,
OHKAWARA S.,
MAEDA T.,
TAKAGI K.,
YOSHINAGA M.
Publication year - 1993
Publication title -
clinical & experimental immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.329
H-Index - 135
eISSN - 1365-2249
pISSN - 0009-9104
DOI - 10.1111/j.1365-2249.1993.tb07967.x
Subject(s) - arthritis , lipopolysaccharide , interleukin 1 receptor antagonist , receptor antagonist , elastase , immunology , endocrinology , medicine , inflammatory arthritis , chemistry , inflammation , receptor , antagonist , enzyme , biochemistry
SUMMARY Injection of lipopolysaccharide (LPS) into rabbil 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‐IRa) 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‐IRa peaked at 9 h (34.5 ± 13.4 ng/joint). The amount of IL‐IRa was 180–200‐fold molar excess of IL‐1, and a large amount of IL‐IRa was sustained for I week. Both IL‐1β and IL‐IRa 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‐IRa. 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‐1 Ra 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.