Granulocyte colony-stimulating factor decreases tumor necrosis factor production in whole blood: role of interleukin-10 and prostaglandin E(2)

Previous reports have indicated that the administration of granulocyte colony-stimulating factor (G-CSF) decreases ex vivo tumor necrosis factor (TNF) production in humans. In this study, we report that daily pretreatment of mice with G-CSF for three days decreases ex vivo lipopolysaccharide (LPS)-induced TNF production in whole blood. Conversely, production of interleukin-10 (IL-10) and prostaglandin E(2) (PGE(2)) is increased. The inhibitory effect of G-CSF pretreatment on TNF production is partially reversed by addition of an anti-IL-10 antibody, and completely reversed by combined addition of anti-IL-10 antibody and the cyclooxygenase (COX) inhibitor, ketoprofen. These results suggest that G-CSF decreases TNF production in this experimental model by increasing production of IL-10 and PGE(2), which are both known inhibitors of TNF production.