title: Lymphocyte apoptosis is resistant to erythropoietin in porcine endotoxemia.
abstract: Sepsis-induced lymphocyte apoptosis plays an important role in the development of immune suppression in septic patients. Erythropoietin (EPO) is a multifunctional cytokine with antiapoptotic properties. We hypothesized that EPO could mitigate mononuclear cell (MNC) apoptosis and modify the dynamic changes of MNCs during endotoxemia. Twenty-six pigs were randomized into three groups: (i) lipopolysaccharides (LPS), (ii) EPO (epoetin-α, 5000 IU/kg) administered 60 min prior to LPS, and (iii) sham. At 120 min of endotoxemia, the animals were fluid resuscitated and the LPS infusion was reduced. MNCs were isolated at 0, 60, 240, and 540 min of endotoxemia, and apoptosis was assessed by flow cytometry. Apoptosis in splenic biopsies was quantified by immunohistochemistry. Endotoxemia increased the number of apoptotic MNCs in the blood (p ≤ 0.01) and the spleen (p = 0.03), and EPO did not modify this increase. The number of T-helper and cytotoxic T cells declined during endotoxemia. The dynamic changes of the MNC subsets were not modified by treatment with EPO. In conclusion, EPO did not modify the LPS-induced changes of MNC subsets or mitigate the levels of apoptosis of MNCs in the blood or in the spleen. This study does not support that EPO confers protection against lymphocyte apoptosis.
authors.affiliation: Department of Anesthesiology and Intensive Care Medicine, Aarhus University Hospital, Denmark. solling@ki.au.dk
authors.forename: Christoffer
authors.initials: C
authors.lastname: Sølling
authors.forename: Uffe
authors.initials: U
authors.lastname: Nygaard
authors.forename: Anton T
authors.initials: AT
authors.lastname: Christensen
authors.forename: Lise
authors.initials: L
authors.lastname: Wogensen
authors.forename: Jan
authors.initials: J
authors.lastname: Krog
authors.forename: Else K
authors.initials: EK
authors.lastname: Tønnesen
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000032:analysis; D019446:Endotoxemia / Q000097:blood*; D004921:Erythropoietin / Q000494:pharmacology*; D005260:Female; D007958:Leukocyte Count; D008214:Lymphocytes / Q000187:drug effects* / Q000502:physiology; D011994:Recombinant Proteins; D013552:Swine
chemical_list: D011994:Recombinant Proteins; D004921:Erythropoietin; D053148:Caspase 3