Colony stimulating factors regulate nitric oxide and prostaglandin E-2 production in rat cartilage chondrocytes

Colony stimulating factors (CSFs) are now widely used in cancer treatment a nd immunological disease therapy Both granulocyte CSF (G-CSF) and granulocy te-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 ox ide and prostaglandin E-2 (PGE(2)) by cartilage explants were examined over 24 and 48 h. The effects of these CSFs were also measured in combination w ith IL-1 beta (10 ng/ml). M-CSF; GM-CSF and IL-3 had no effect on nitrite p roduction. However both IL-1 beta and G-CSF caused a significant increase ( p <0.05) in nitrite levels at 48 h. N-G-L-arginine-methyl-ester was used to inhibit nitrite production induced by G-CSF and this implicated nitric oxi de synthase activity When G-CSF and IL-1 beta were used in a combined treat ment, 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 PGE , production in this model. PGE(2) levels were also significantly increased by stimulation with GM-CSF and IL-3 combined with IL-1 beta. These finding s demonstrate that GM-CSF, G-CSF and IL-3 may induce changes in the product ion of inflammatory mediators such nitric oxide and PGE(2) in cartilage cho ndrocytes. Hence, CSFs may play a vital role in influencing cartilage metab olism in rheumatoid and osteoarthritis.