Despite advances in understanding and treatment of sepsis, it remains a disease with high mortality. Neutrophil Derived Microparticles (NDMPs) are present during sepsis and can modulate the immune system. As TNF-alpha is a cytokine that predominates in the initial stages of sepsis, we evaluated whether and how TNF-alpha can induce NDMPs in mice. We observed that TNF-alpha treatment results in increased NDMP numbers. We also determined that the activation of either TNF receptor 1 (TNFr1) or TNF receptor 2 (TNFr2) resulted in increased NDMP numbers and that activation of both resulted in an additive increase. Inhibition of Caspase 8 diminishes NDMPs generated through TNFr1 activation and inhibition of NF-kappa B abrogates NDMPs generated through activation of both TNFr1 and TNFr2. We conclude that the early production of TNF-alpha during sepsis can increase NDMP numbers through activation of the Caspase 8 pathway or NF-kappa B. (C) 2013 Elsevier Inc. All rights reserved.