Pro- and anti-inflammatory properties of human recombinant IL-1 beta during experimental arthritis in rats: 1. Dependence on dose and severity threshold.
The effects of human recombinant interleukin-1 beta (HrIL-1 beta) were investigated in arthritic rats sensitized with type II collagen (CII) and muramyl dipeptide (MDP). When administered subcutaneously (sc) daily during established arthritis, low (0.02 micrograms) and medium (0.2 micrograms) HrIL-1 beta doses exerted paradoxical beneficial properties on paws with moderate and severe inflammation, respectively. In contrast, the highest dose (2 micrograms) had a pejorative effect on developing arthritis. In addition, HrIL-1 beta attenuated paw volume and deterioration of the joints as assessed radiologically. Hence, paw inflammation response to IL-1 exposure depended on the dosage and the severity of previous arthritis prior to the IL-1 challenge. Some of these paradoxical activities may be due to the capacity of IL-1 to induce its own inhibitors or feedback loops thus counterbalancing its phlogistic properties.
Drelon
E
E
Laboratoire de Pharmacologie, URA CNRS 1288, Faculté de Médecine, Nancy, France.
Jouzeau
J Y
JY
Gillet
P
P
Gegout
P
P
Chevrier
D
D
Terlain
B
B
Netter
P
P
D000818:Animals; D001168:Arthritis / Q000000981:diagnostic imaging / Q000188:drug therapy*; D001835:Body Weight / Q000187:drug effects; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005260:Female; D007375:Interleukin-1 / Q000008:administration & dosage / Q000494:pharmacology*; D011859:Radiography; D051381:Rats; D011920:Rats, Inbred WF; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000494:pharmacology; D012720:Severity of Illness Index
D007375:Interleukin-1; D011994:Recombinant Proteins