Colony stimulating factors regulate nitric oxide and prostaglandin E2 production in rat cartilage chondrocytes

Colony stimulating factors (CSFs) are now widely used in cancer treatment and immunological disease therapy. Both granulocyte CSF (G-CSF) and granulocyte-macrophage CSF (GM-CSF) are used to increase neutrophil counts in Felty syndrome. In the present study, the effects of macrophage CSF (M-CSF), G-CSF, GM-CSF and interleukin-3 (IL-3) (10 ng/ml) on the production of nitric oxide and prostaglandin E2 (PGE2) by cartilage explants were examined over 24 and 48 h. The effects of these CSFs were also measured in combination with IL-1 beta (10 ng/ml). M-CSF, GM-CSF and IL-3 had no effect on nitrite production. However, both IL-1 beta and G-CSF caused a significant increase (p < 0.05) in nitrite levels at 48 h. NG-L-arginine-methyl-ester was used to inhibit nitrite production induced by G-CSF and this implicated nitric oxide synthase activity. When G-CSF and IL-1 beta were used in a combined treatment, nitrite levels were significantly increased (p < 0.05) at both 24 and 48 h. Both IL-3 alone and in combination with IL-1 beta caused elevated PGE2 production in this model. PGE2 levels were also significantly increased by stimulation with GM-CSF and IL-3 combined with IL-1 beta. These findings demonstrate that GM-CSF, G-CSF and IL-3 may induce changes in the production of inflammatory mediators such nitric oxide and PGE2 in cartilage chondrocytes. Hence, CSFs may play a vital role in influencing cartilage metabolism in rheumatoid and osteoarthritis.