GRANULOCYTE-MACROPHAGE COLONY-STIMULATING FACTOR EXACERBATES COLLAGEN-INDUCED ARTHRITIS IN MICE

Objective-To examine the effect of granulocyte-macrophage colony stimu lating factor (GM-CSF) on disease progression in the collagen induced arthritis (CIA) model in mice. Methods-DBA/1 mice were primed for a su boptimal CIA response by intradermal injection of chick type II collag en without a secondary immunisation. Three weeks after immunisation th e mice were given four to five consecutive daily intraperitoneal injec tions of recombinant murine GM-CSF (15 mu g; 5 x 10(5) U), or vehicle, and arthritis development was monitored by clinical scoring of paws a nd calliper measurements of footpad swelling. At approximately six to eight weeks after immunisation mice were killed, their limbs removed a nd processed for histological analyses of joint pathology. Results-Con trol animals receiving a single immunisation with collagen exhibited a varied CIA response both in terms of incidence and severity. Mice tre ated with GM-CSF at 20 to 25 days after immunisation with collagen had a consistently greater incidence and more rapid onset of disease than the vehicle treated control mice, based on clinical assessment. GM-CS F treated mice showed higher average clinical scores and greater paw s welling than controls. Histological analyses of joints reflected the c linical scores with GM-CSF treated mice displaying more pronounced pat hology (synovitis, pannus formation, cartilage and bone damage) than c ontrol mice. Conclusion-GM-CSF is a potent accelerator of the patholog ical events leading to chronic inflammatory polyarthritis in murine CI A supporting the notion that GM-CSF may play a part in inflammatory po lyarthritis, such as rheumatoid arthritis.