Immunopharmacological studies on collagen-induced arthritis in dark Agouti (DA) rats.

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.