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Prevention of sepsis by correcting apoptosis


Activation of apoptosis in lymphocytes determines the development of neutropenia and of sepsis [1, 2]. We investigated prevention of sepsis and correction of lymphocyte apoptosis by recombinant human granulocyte colony-stimulating factor (hr-GCSF, fillgrastim) [1, 2].


With the permission of the ethics committee, a controlled, randomized, blind clinical trial included 69 term newborns on mechanical ventilation, without neutropenia and clinical signs of infection, with a content of lymphocytes in early apoptosis (AnnexinV-FITC+PI-) of >9.59%, and in late (AnnexinV-FITC+PI+) of 0.56%. Lymphocytes in apoptosis were detected using antibodies to AnnexinV and propidium iodide staining method of immunophenotyping (flow cytometry; Beckman Coulter Epics XL, USA). The survey was conducted at admission, at 3 to 5 days, and 20 days. The method of random numbers in Group I included 39 newborns who on admission (with written parental consent) received an intravenous infusion of hr-GCSF dose of 10 μg/kg, 3 days. Newborns of Group II (n = 30) did not receive hr-GCSF. Power of the study was 80% (α ≤ 0.05).


For 3 to 5 days, Group I significantly decreased apoptosis of lymphocytes in the early from 16.1% to 7.8%, and in late from 1.3% to 0.1%. The development of sepsis and neutropenia have been reported. We observed no clinical or laboratory signs of adverse effects of the drug. Fatal outcomes (n = 4) are not associated with hr-GCSF, which was confirmed postmortem. Decreased duration of mechanical ventilation (P < 0.05). In Group II, 27 patients at 3 to 5 days developed neutropenia and increased lymphocytes in apoptosis (P < 0.05). Sepsis was diagnosed in 19 children; eight fatal outcomes.


hr-GCSF reduces the incidence of septic complications and one of the mechanisms of its clinical effectiveness is the reduction of apoptotic factors affecting the development of neutropenia.


  1. Gillan ER, Christensen RD, Suen Y, et al.: A randomized, placebo-controlled trial of recombinant human granulocyte colony-stimulating factor administration in newborn infants with presumed sepsis: significant induction of peripheral and bone marrow neutrophilia. Blood 1994, 84: 1427-1433.

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  2. Pukhtinskaya MG, Estrin VV, Gulova ES: Clinical and diagnostic value of apoptosis markers in the pathogenesis of neutropenia and bacterial complications in newborns with respiratory distress syndrome. Cytokines Inflamm 2011, 10: 66-69.

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Puhtinskaya, M., Estrin, V. Prevention of sepsis by correcting apoptosis. Crit Care 17 (Suppl 2), P8 (2013).

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