Pro- and anti-inflammatory roles of interleukin-1 in recurrence of bacterial cell wall-induced arthritis in rats.
A specific interleukin-1 (IL-1) receptor antagonist (IL-1ra) was used to examine the roles of IL-1 in an experimental model designed to analyze the reactivation phase of erosive arthritis, induced in rats with peptidoglycan-polysaccharide polymers (PG-APS) isolated from cell walls of group A streptococci. Monoarticular arthritis was initiated by injection of a small dose of PG-APS into an ankle joint, and reactivation was induced by intravenous injection of PG-APS 20 days later. Human recombinant IL-1ra given at a dose of 2 to 3 mg/kg at the time of reactivation of arthritis and at 6-h intervals inhibits the increase in joint swelling by at least 60%. Joint swelling is suppressed 30 to 50% when the initial treatment with IL-1ra is delayed until 6 h after reactivation. IL-1ra is not effective when the initial injection is delayed 12 or 24 h. With an injection schedule of IL-1ra given at the time of reactivation and every 6 h, treatment can be stopped at 24 h and the suppression of swelling is no different from that in rats for which injections are continued for 4 days. The results indicate that IL-1 has a prominent, although not exclusive, role in initiating inflammation in this model and is involved in the amplifying processes in progressive inflammation and chronic erosive disease. An anti-inflammatory function of IL-1 is also indicated from data showing that IL-1ra treatment limited to 6 h or less after the induction of reactivation enhances joint swelling, whereas intravenous injection of human recombinant IL-1 beta 24 h before reactivation suppresses the reactivation of arthritis.
Schwab
J H
JH
Department of Microbiology and Immunology, University of North Carolina School of Medicine, Chapel Hill 27599.
Anderle
S K
SK
Brown
R R
RR
Dalldorf
F G
FG
Thompson
R C
RC
D000818:Animals; D001170:Arthritis, Infectious / Q000209:etiology* / Q000473:pathology / Q000517:prevention & control; D002473:Cell Wall; D005260:Female; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1 / Q000502:physiology*; D007596:Joints / Q000473:pathology; D010457:Peptidoglycan; D011108:Polymers / Q000494:pharmacology; D011506:Proteins / Q000494:pharmacology; D051381:Rats; D011917:Rats, Inbred Lew; D012008:Recurrence; D012795:Sialoglycoproteins
C507763:IL1RN protein, human; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1; D010457:Peptidoglycan; D011108:Polymers; D011506:Proteins; D012795:Sialoglycoproteins