Perioperative Infektionsprophylaxe mit G-CSF steigert die Konzentration anti-inflammatorischer Zytokine bei Patienten mit Ösophaguskarzinom

Abstract

Objectives: During the last 30 years, the incidence of esophageal cancer has increased substantially. Despite antibiotic therapy and improved intensive care patients undergoing esophagectomy are at high risk for severe postoperative infection. The aim of this interim analysis of an ongoing phase III study was to investigate the effects of G-CSF (granulocyte colony stimulating factor) treatment on cytokine profiles. Materials and Methods: In a prospective randomised controlled trial, 44 patients were treated perioperatively, from 2 days before to day 7 after operation, with G-CSF (Filgrastim, 300 µg ≤ 75 kg or 480 > 75 kg) or placebo. Serum samples were collected on day-2, 0, 3, 6 and 10. G-CSF, IL-1ra, IL-8 and sTNFRp55 levels were measured using highly specific ELISA kits. Results G-CSF showed a substantial increase from 28.4 to a maximum of 2363 pg/ml at day 0 in the treatment group (maximum 100 pg/ml in control). IL-1ra increased to a maximum of 6150 pg/ml in treatment versus 1764 pg/ml in control patients. TNF receptors increased from 2983 to 12880 pg/ml at day 1 (4980 pg/ml in controls). IL-8 decreased by a factor of 6 in both groups. The comparison of the study and the control group showed significant differences for G-CSF, sTNFRp55 and IL1ra (p < 0.05). Conclusions: Anti-inflammatory cytokines G-CSF, sTNFRp55 and IL1ra showed a significant increase in the treatment group. In contrast, there was a decrease of the proinflammatory cytokine IL-8 levels detectable. The induction of anti-inflammatory cytokines and the downregulation of proinflammatory cytokines by G-CSF might be a successful approach to prevent infectious complications in patients undergoing esophagectomy.