University of California, Irvine Irvine United States
Tumor Necrosis Factor-alpha TNF is elevated in myeloproliferative neoplasm MPN and plays a key role in expansion of the JAK2V617F neoplastic clone. We have found that MPN monocytes produce excessive amounts of TNF in response to TLR ligation due to a defect in the negative regulatory feedback loop which normally serves to dampen TNF production. We have localized this defect to a blunted response to the anti-inflammatory cytokine IL-10. MPN monocytes are less responsive to the anti-inflammatory actions of IL-10 at low concentrations but these effects can be restored by increasing the concentration of IL-10.Together, these data suggest that administration of IL-10 may reduce excessive inflammatory cytokine production in MPN.