Effects of murine recombinant interleukin 1 on intact homologous articular cartilage: a quantitative and autoradiographic study.

Abstract

Murine recombinant interleukin 1 (IL1) was tested for its ability to affect intact murine articular cartilage. IL1 caused enhanced proteoglycan degradation and severe inhibition of chondrocyte synthetic function at a concentration of 3 U/ml (100 pg/ml). Inhibition of proteoglycan synthesis appeared to be delayed in onset but occurred consistently after 24 hours. Pulse chase experiments made it clear that proteoglycan degradation and inhibition of proteoglycan synthesis are two distinct actions of IL1. No indications were obtained for selective degradation of either newly synthesised or processed proteoglycan. Moreover, chondrocyte synthetic activity appeared to be inhibited uniformly throughout the cartilage matrix, i.e., no evidence was found for selective suppression of cells in certain regions. IL1 uptake measurement in the cartilage, using [125I]IL1, yielded a partition coefficient far below 1, and autoradiography demonstrated a faint but even distribution within the cartilage matrix. The coordinated induction of enhanced breakdown of proteoglycan and inhibition of proteoglycan synthesis, with such low concentrations of IL1 reaching the chondrocytes, underlines the impressive destructive potential of IL1.