CYTOKINE PRODUCTION IN SYNOVIAL TISSUE OF MICE WITH COLLAGEN-INDUCED ARTHRITIS (CIA)

The kinetics of cytokine production in arthritic limbs of mice with CI A was determined by using modified immunohistochemical techniques. Tis sue cryostat sections of undecalcified whole paws were analysed for th e presence of tumour necrosis factor-alpha (TNF-alpha), IL-6, IL-2, IL -4, IL-5 interferon-gamma (IFN-gamma), transforming growth factor-beta 2 (TGF-beta 2) and TGF-beta 3. Locally produced TNF-alpha, IL-6 and T GF-beta 2 were observed within the lining layer, sublining and pannus at all stages of disease. The staining of TNF-alpha was particularly i ntense at the cartilage-pannus junction. In contrast to the monokines, IFN-gamma and TGF-beta 3 were only expressed in scattered cells withi n the deeper layers of the synovia. Interestingly, IFN-gamma was not p resent in the late phase of CIA, despite the continued presence of TNF -alpha and IL-6 in the pannus. Production of IL-2, IL-4 or IL-5 was no t detected in any joint. The observed pattern of a relative paucity of T cell-derived cytokines and an abundance of monokines during the lat e phase of T cell-dependent CIA indicates that the synovial cytokine p attern previously described in rheumatoid arthritis (RA) is fully comp atible with a pathogenic role of T cells. The temporal as well as spat ial dissociation between expression of T cell-derived cytokines and mo nokines indicates that T cell-independent mechanisms may also be of im portance in the triggering of monokine production during arthritis.