Immunopharmacological Studies on Collagen-Induced Arthritis in Dark Agouti (DA) Rats
Hiroyuki Kamada, Moritaka Goto, Satoko Matsuura, Yuko Takaoka and Hiroichi
Nagai
Department of Pharmacology, Gifu Pharmaceutical University, 5-6-1 Mitahora-higashi,
Gifu 502, Japan
Abstract: Dark Agouti (DA) and Lewis rat strains were tested
for susceptibility to collagen-induced arthritis (CIA) and for development
of cellular and humoral immune responses to type II collagen (CII). All
of the DA rats developed arthritis following a single intradermal injection
of more than 20 microg of CII (130 - 150 microg/kg rat weight) and showed
a swelling rate of more than 100% in the hind paws. The swelling rate showed
little deviation among the animals. There was a strong correlation between
the severity of the arthritis and the strength of the immune response to
CII in DA rats with CIA. Following immunization with even 800 microg of
CII (3.8 - 4.2 mg/kg rat weight), Lewis rats showed a maximum rate of hind
paw swelling of only 45%. In the pharmacological studies, prednisolone,
indomethacin, FK-506 and mizoribine all suppressed arthritis in DA rats.
These findings suggest that DA rats are more susceptible to CIA than Lewis
rats and that CIA in DA rats as well as in Lewis rats is serviceable as
an experimental animal model of rheumatoid arthritis.
Keywords: Dark Agouti (DA) rat, Collagen-induced arthritis, Anti-rheumatic
drug