Prostaglandin E2 and collagenase production by fibroblasts and synovial cells is regulated by urine-derived human interleukin 1 and inhibitor(s).

Abstract

Interleukin 1 (IL-1) possesses multiple biological activities that may be blocked selectively by different inhibitors. Some known inhibitors block the lymphocyte activating factor (LAF/IL-1) but not the mononuclear cell factor (MCF/IL-1) measured by its capacity to stimulate prostaglandin E2 (PGE2) and colingenase production. The presence of IL-1 in vivo may be difficult to detect due to the presence of inhibitor(s) and the level of the inhibitor(s) may vary depending upon pathological conditions. We have found that urine from three patients with monocytic leukemia (M5) contained high levels of inhibitor(s) of MCF/II-1, whereas urine of normal subjects did not contain significant amounts. Urine from two patients with other blood neoplasic diseases also contained little inhibitory activity. The MCF/IL-1 inhibitor(s), which also acts on human recombinant IL-1 ft, is -25-35 kD, is not retained on concanavalin A-Sepharose column and can be partially destroyed with urea and boiling. At this stage of the purification the fraction containing the MCF/IL-1 inhibitor(s) also inhibits the LAF/IL-1 assay. However, this inhibitor(s) is probably distinct from other inhibitors already described.

Activation of the peroxisome proliferator–activated receptor α pathway potentiates interleukin‐1 receptor antagonist production in cytokine‐treated chondrocytes

“…The expression of collagenase and production of PGE 2 are suppressed by sIL-1Ra in synoviocytes in vitro (36). Administration of sIL-1Ra in vivo in an experimental arthritis model was also shown to exert protective effects.…”

The pivotal role of interleukin-1 in the clinical manifestations of rheumatoid arthritis

“…Our attention also focused on diseases with spontaneous remission of fever, since we suspected the presence of natural inhibitors that reversed the peak of fever. To our surprise, we failed to detect any biological activity of IL-1 in serum or urine of seriously ill patients with one of the above diseases [36][37][38]. This gave rise to the hypothesis that IL-1 activity may be masked by an inhibitory molecule and that concentrations of such an inhibitory molecule must be considerably elevated during fever remission.…”

Modulation of the effects of interleukin‐1 on glycosaminoglycan synthesis by the urine‐derived interleukin‐1 inhibitor, but not by interleukin‐6

“…The inhibitor was originally identified in the urine of patients with monocytic leukemia (12,13) and is probably similar to the inhibitor present in patients with juvenile rheumatoid arthritis (14). Specific for IL-I, it is effective against rHuIL-la and rHuIL-lP, whereas tumor necrosis factor a (TNFa) activities shared with IL-1 are unaffected by it (15).…”