Effects of human recombinant tumor necrosis factor-α and interleukin 1 on the synthesis of glycosaminoglycan and DNA in cultured rat costal chondrocytes

We examined effects of human rTNFα on the synthesis of glycosaminoglycan and DNA in cultured rat costal chondrocytes. The effects of human recombinant IL-1α and IL-1β were also given attention. rTNFα, as well as rIL-1α and rIL-1β, decreased the incorporation of [³⁵S]sulfate into glycosaminoglycan to about 10% of the levels in the control. The half-maximal doses of rTNFα, rIL-1α or rIL-1β required for the suppression of glycosaminoglycan synthesis (by rTNFα, rIL-1α, and rIL-1β) were 2 ng/ml, 30 ng/ml, or 5 ng/ml, respectively. rTNFα stimulated incorporation of [³H]thymidine in the chondrocytes in a dose- and time-dependent manner. DNA synthesis was increased to about threefold over the control cultures in the presence of μg/ml rTNFα for 72 hr. The stimulatory effect of rTNFα on DNA synthesis was observed in both subconfluent and confluent cultures, whereas rIL-1α and rIL-1β had no stimulatory activity on DNA synthesis. The addition of rTNFα to the cultures of chondrocytes stimulated DNA synthesis, even in medium containing no fetal calf serum. The fetal calf serum acted synergistically with rTNFα in increasing DNA synthesis. We propose that both TNF and IL-1 may be involved in inflammatory diseases of cartilage, and that TNFα, but not IL-1, may have some physiologic growth factor function for chondrocytes.