Systemic anti-inflammation by synthetic interleukin-1 blockers.
OBJECTIVE
To study the systemic anti-inflammatory actions of interleukin-1 (IL-1) blockers, OB-101 and OB-186.


METHODS
Prevention of palm swelling induced by carrageenin injection was used as an animal model of systemic anti-inflammation efficacy.


RESULTS
Both OB-101 and OB-186 (10-30 mg.kg-1) were approximately 10-30-fold more potent than aspirin (300 mg.kg-1) to inhibit carrageenin-induced systemic inflammation. The LD50 of OB-101 and OB-186 were at least 20 g.kg-1 i.g., indicating that they were extremely safe agents with a therapeutic index (LD50/ED50) of at least 2000.


CONCLUSIONS
These IL-1 blockers are extremely safe systemically and are useable for the treatment of systemic inflammation such as rheumatoid arthritis.
Chiou
G C
GC
Department of Medical Pharmacology and Toxicology, College of Medicine, Texas A & M University, College Station 77843, USA. gchiou@tamu.edu
Liu
S X
SX
D000166:Acridines / Q000627:therapeutic use*; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use*; D001241:Aspirin / Q000627:therapeutic use; D005260:Female; D007097:Imines / Q000627:therapeutic use*; D007249:Inflammation / Q000139:chemically induced / Q000188:drug therapy*; D007375:Interleukin-1 / Q000037:antagonists & inhibitors*; D007928:Lethal Dose 50; D008297:Male; D051379:Mice; D011817:Rabbits; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D013843:Thiazines / Q000627:therapeutic use*
D000166:Acridines; D000894:Anti-Inflammatory Agents, Non-Steroidal; D007097:Imines; D007375:Interleukin-1; D013843:Thiazines; C097967:CK 102; C091704:CK 17; D001241:Aspirin