Einfluss von Wachstumsfaktoren auf den Respiratory Burst humaner neutrophiler Granulozyten lebertransplantierter Patienten in vitro

Abstract

Early post-operative infections remain the most important cause of morbidity and mortality in patients following orthotopic liver transplantation (OLTx). Since polymorphonuclear neutrophils (PMNs) are one of the major determinants of antimicrobial defence, the alteration of their functions may influence the outcome of infection in these patients. Ciclosporin predominantly used as immunosuppressive drug following organ transplantation inhibits superoxide anion production during respiratory burst (RB) of PMNs. Growth factors have been shown to modulate the RB of PMNs in healthy volunteers. It has been examined whether PMNs from patients under immunosuppression following OLTx can be primed by in vitro administration of interleukin-3 (IL-3), granulocyte-macrophage colony stimulating factor (GM-CSF), and granulocyte colony stimulating factor (G-CSF). For flow-cytometric evaluation, leukocytes were obtained as supernatant following sedimentation and were incubated with IL-3 (500 U ml-1), IL-3 and GM-CSF (500 U ml-1), or IL-3 and G-CSF (500 U ml-1). The RB was measured by intracellular oxidation of non-fluorescent dihydrorhodamine to green fluorescent rhodamine after induction of phorbol 12-myristate 13-acetate (PMA) or a combination of tumour necrosis factor alpha (TNF-alpha) and N-formyl-methionyl-leucyl-phenylalanine (FMLP). Following stimulation with PMA, the RB of patients following OLTx could be increased significantly after priming with the combination of IL-3/G-CSF (p < 0.03); following stimulation with TNF-alpha/FMLP the RB could be increased significantly by IL-3 (p < 0.01), IL-3/G-CSF (p < 0.002), and IL-3/GM-CSF (p < 0.002). Regarding the clinical administration of IL-3, GM-CSF and G-CSF following OLTx, the role of these cytokines for prophylaxis or treatment of early postoperative infections should be further investigated.