Effect of the immunomodulating agent, pentoxifylline, in the treatment of sepsis in prematurely delivered infants: A placebo-controlled, double-blindtrial

Objective: To evaluate the influence of the methylxanthine derivative, pent oxifylline, on plasma levels of tumor necrosis factor (TNF)-alpha interleuk in (IL)-1, and IL-6 in prematurely delivered infants with generalized bacte rial infections and to assess the effect of this immunomodulating drug on t he clinical outcome in newborns with sepsis, Design: A prospective, randomized, double-blind trial. Setting: The neonatal intensive therapy units in university teaching hospit als. Patients: One hundred patients with sepsis admitted during a 1.5 yr period, Interventions: Patients were randomly assigned to receive pentoxifylline (p entoxifylline group) in a dose of 5 mg/kg/hr for 6 hrs on 6 successive days or an identically presented placebo (placebo group). Measurements and Main Results: Only infants with sepsis confirmed by positi ve blood culture were recruited into the study, There were no significant d ifferences at randomization between the pentoxifylline and placebo groups w ith regard to the birth weight, gestational age, gender, Apgar score, hypot ension, neutropenia, thrombocytopenia, metabolic acidosis, plasma levels of cytokines, and occurrence of shock, Plasma levels of TNF, IL-l, and IL 6 w ere evaluated before and after the drug or placebo administration on the fi rst, third, and sixth days of therapy. Cytokines were determined by immunoe nzymetric test EASIA (TNF) and Endogen Interleukin Elisa (IL-1, IL-6), The frequency of Gramnegative sepsis was similar in both groups (37.5% and 36.8 %), Pentoxifylline significantly diminished plasma TNF levels (p =.009) but had no effect on plasma IL-l levels. Mean plasma IL-6 levels, which were m easured in the pentoxifylline group on the 6th day of the study, were signi ficantly lower compared with respective data obtained in the placebo group. Only 1 of 40 infants with sepsis in the pentoxifylline group died, whereas 6 of 38 infants in the placebo group did not survive (p =.046), An increas ed incidence of disordered peripheral circulation and metabolic acidosis (p =.048), anuria or oliguria (p =.03), disseminated intravascular coagulatio n (p =.043), and the occurrence of clinical symptoms of necrotizing enteroc olitis (p =.025) was observed in the course of sepsis in infants in the pla cebo group. Conclusion: Pentoxifylline significantly affects the synthesis of TNF and I L 6 as well as reduces the mortality rate in premature infants with sepsis, The dosage and schedule of drug administration in this study attenuated th e severity of the clinical course of sepsis in this group of patients.