The M20 IL-1 inhibitor prevents onset of adjuvant arthritis.
Cytokines, specifically IL-1 and TNF, have been implicated as important mediators of joint destruction in rheumatoid arthritis (RA). Elevated levels of IL-1 in the joint fluid of patients with RA have been reported, as well as the presence of IL-1 inhibitory activity. We have reported the characterization of an inhibitor derived from a myelomonocytic cell line cloned in our laboratory which is specific for IL-1. This IL-1 inhibitor is protein in nature which specifically inhibits activity in vitro and in vivo. Previous studies showed that the inhibitor reduced acute inflammatory reactions associated with IL-1 (fever, leukocytosis, local foot pad swelling, lymph node enlargement and acute phase reactants). Thus it was of interest to study whether the M20 IL-1 inhibitor could modify adjuvant-induced chronic inflammation in rats, which is often used as a model for human RA. Administration of complete Freund's adjuvant (CFA) into Lewis rats, resulted in a severe adjuvant arthritis (AA) which reached peak severity after 14 days. Daily administration of IL-1 inhibitor, beginning after injection of CFA, abolished the appearance of AA. The parameters investigated were: joint swelling (the increase in diameter of joints), peri-articular erythema, limping of the rats and histological examination. The effect of the M20 IL-1 inhibitor was shown to be dose dependent and the IL-1 inhibitor alone had no adverse effects. These results indicate that the M20 IL-1 inhibitor may have a role in the treatment of AA and may be used to reduce pathological processes in joint inflammation.
Vivian
B
B
Department of Oncology, Hadassah Hospital Ein Kerem, Jerusalem, Israel.
David
P
P
Iancu
F
F
Yoav
S
S
Elimelech
O
O
Peter
Y
Y
Tal
H
H
Trevis
A J
AJ
D000818:Animals; D001169:Arthritis, Experimental / Q000473:pathology / Q000517:prevention & control*; D001831:Body Temperature; D002457:Cell Extracts / Q000627:therapeutic use; D002460:Cell Line; D005121:Extremities; D006801:Humans; D007375:Interleukin-1 / Q000037:antagonists & inhibitors*; D007719:Knee Joint / Q000473:pathology; D051381:Rats; D011917:Rats, Inbred Lew
D002457:Cell Extracts; D007375:Interleukin-1