Modulation of connective tissue metabolism by partially purified human interleukin 1

We have investigated the relationship between the monokine interleukin 1 (IL-1) and the connective tissue-stimulating activities produced by monocytes such as mononuclear cell factor (MCF). Using almost exclusively human tissue we have monitored a wide range of MCF-like activities through the partial purification of IL-1 by gel filtration and isoelectric focusing. Activities measured include stimulation of chondrocytes to produce prostaglandins, plasminogen activator and proteoglycanase, enhancement of synovial cell proliferation, and stimulation of cartilage resorption, in addition to IL-1 (lymphocyte activating factor) activity. The activities described show the same molecular heterogeneity; the active material has similar potencies in the different systems, and removal of IL-1 activity by pretreatment with phenylglyoxal also results in loss of the connective tissue-stimulating activities. These results show that the factors responsible for this wide range of activities are very closely related to IL-1 and give further evidence in support of the possible involvement of IL-1 in the processes of joint destruction occurring in chronic inflammatory conditions such as rheumatoid arthritis.