Granulocyte-macrophage colony stimulating factor is anabolic and interleukin-1beta is catabolic for rat articular chondrocytes.

OBJECTIVE

To study the effects of GM-CSF and IL-1beta, both implicated in tissue damage in arthritis, on articular chondrocyte proliferation and metabolism, and to explore their agonist/antagonist effects.

METHODS

Chondrocytes were obtained from 1-month-old rats. First-passage monolayers were incubated for 24 h with or without GM-CSF and/or IL-1beta, and labeled with 3H-thymidine, 35S-SO4 and 14C-proline. Proteoglycan and collagen synthesis were analyzed by liquid chromatography and SDS-PAGE. Gene expression was measured by RT-PCR.

RESULTS

IL-1beta exerts potent, and GM-CSF weak, inhibitory effects on DNA synthesis. GM-CSF strongly stimulates, and IL-1beta inhibits, proteoglycan and collagen synthesis. IL-1beta suppresses the effect of GM-CSF, and increases the release of radioactive molecules from pre-labeled cartilage fragments; GM-CSF decreases the IL-1beta-induced effect. Interestingly, both cytokines induce the expression of each other's gene.

CONCLUSIONS

IL-1beta appears to be a catabolic and anti-anabolic agent for chondrocytes, whereas GM-CSF is mainly anabolic, and blocks the IL-1beta-induced catabolic effect. It is postulated that both agents are implicated in inflammation: IL-1beta promotes tissue catabolism and destruction, whereas GM-CSF enhances tissue reconstruction.