STIMULATION OF CHONDROCYTE DNA SYNTHESIS BY INTERLEUKIN-1

Abstract

Interleukin-1 (IL-l)-containing conditioned media (CM) from activated guinea-pig peritoneal macro-phages were found to stimulate the DNA synthesis of rat epiphyseal chondrocytes in vitro. Sephadex G 150 chromatography revealed that the chondrocyte-stimulating activity was molecularly heterogeneous, with apparent molecular ratios of 16 000-21 000 (16-21K), 45-50K, 80-90K, and more than 100K. The IL-1 activity, as estimated by a murine thymocyte activation assay, co-eluted with the 16-21K chondrocyte-stimulating peak, indicating that IL-1 might stimulate the DNA synthesis of chondrocytes in vitro. This assumption was verified in experiments demonstrating a dose-dependent stimulation of chondrocyte DNA synthesis by recombinant human IL-1 a. CM from resting and proliferating chondrocytes lacked detectable IL-1 activity, speaking against an autocrine role of IL-1 in epiphyseal cartilage growth. The results suggest that IL-1, in addition to its other effects in inflammatory responses, also acts as a chondrocyte growth factor. This might be one mechanism behind the reactive formation of cartilage in inflamed joints and the increased longitudinal bone growth often seen in affected limbs of children with arthritis.