Systemic inflammation in xenograft recipients (SIXR) or undetected PCMV/PRV transmission?

Transplantation of pig organs into non-human primates has often been associated with clinical symptoms described as systemic inflammation in xenograft recipients (SIXR). 1–4 Systemic inflammation precedes andpromotesactivationofcoagulationafterpig-to-nonhumanprimate xenotransplantation, irrespective of immunosuppressive therapy. 3 Inflammation can be described as a complex biological response of an organism to harmful stimuli and chronic inflammation is observed in various diseases, for example, diabetes, infection, or atherosclerosis. 4 Inflammationisassociatedwiththereleaseofawiderangeofcytokines and chemokines, recruiting immune cells to the site of inflammation and modulating the maturation of immune cells. Among these molecules are tumor necrosis factor (TNF) and interleukin 6 (IL-6), which are highly elevated in animals with SIXR. 5 Innate immune cells expressing tissue factor (TF) are activated after xenotransplantation and expression of the TF by activated endothelial cells is an initial mechanism in the development of thrombotic microangiopathy in the transplant and consumptive coagulopathy (CC) in the recipient. 3,6 Thrombotic microangiopathy and CC are characteristic features asso-ciatedwithxenotransplantfailure. 7,8 TNF-alpha 9 andIL-6 10