The effects of interleukin-1 on articular cartilage destruction as observed in arthritic diseases, and its therapeutic control.

At present there is substantial evidence to suggest that interleukin 1 (IL-1) may act as a key mediator in the normal physiologic regulation of cartilage as well as in the pathogenesis of cartilage destruction in arthritic disorders. IL-1 induces stimulation of chondrocyte catabolism and alters chondrocyte biosynthesis in articular cartilage. These actions of IL-1 may lead to destruction and inappropriate repair following degradation of the cartilage matrix. Moreover, IL-1 induced biological activities in chondrocytes may be influenced by growth factors (e.g. fibroblast growth factor, insulin-like growth factor, transforming growth factor-beta), guanine nucleotide proteins, or other cytokines. With respect to the widely suggested potential significance of IL-1 in arthritis, pharmacological control of IL-1 action is of important clinical relevance. Today the therapeutic control of IL-1 induced effects in articular cartilage destruction as observed in arthritic diseases can be divided into drugs which affect IL-1 production, drugs which modify or block the IL-1 effect before stimulation of the target cell, or drugs that interfere with the IL-1 induced effects, e.g. steroidal drugs, non-steroidal anti-inflammatory drugs, immunoregulatory drugs or class-specific proteinase inhibitors. However, these drugs do not specifically block IL-1 activity. For the development of therapeutic agents capable of specifically blocking IL-1 effects, a better understanding of IL-1 induced activities is needed. In conclusion, knowledge about chondrocyte metabolic and regulatory alterations would be beneficial in unraveling the events that take place in arthritic diseases and would favor therapeutic research for agents that might arrest the progressive destruction of articular cartilage in pathological conditions.