Influence of growth factors on the respiratory burst of human neutrophils in patients following liver transplantation in vitro

Early post-operative infections remain the most important cause of morbidit y and mortality in patients following orthotopic liver transplantation (OLT x). Since polymorphonuclear neutrophils (PMNs) are one of the major determi nants of antimicrobial defence, the alteration of their functions may influ ence the outcome of infection in these patients. Ciclosporin predominantly used as immunosuppressive drug following organ transplantation inhibits sup eroxide anion production during respiratory burst (RB) of PMNs. Growth fact ors have been shown to modulate the RE of PMNs in healthy volunteers. It ha s been examined whether PMNs from patients under immunosuppression followin g OLTx can be primed by in vitro administration of interleukin-3 (IL-3), gr anulocyte-macrophage colony stimulating factor (GM-CSF), and granulocyte co lony stimulating factor (G-CSF). For flow-cytometric evaluation, leukocytes were obtained as supernatant following sedimentation and were incubated wi th 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 RE was measured by intracellular oxidation of non-fluore scent dihydrorhodamine to green fluorescent rhodamine after induction of ph orbol 12-myristate 13-acetate (PMA) or a combination of tumour necrosis fac tor alpha (TNF-alpha) and N-formyl-methionyl-leucyl-phenylalanine (FMLP). F ollowing stimulation with PMA, the RE of patients following OLTx could be i ncreased significantly after priming with the combination of IL3/G-CSF (p < 0.93): following stimulation with TNF-<alpha>/FMLP the RE could be increas ed significantly by IL-3 (p < 0.01), IL-3/G-CSF (p < 0.002), and IL-3/GM-CS F (p < 0.002). Regarding the clinical administration of IL-3. GM-CSF and G- CSP following OLTx, the role of these cytokines for prophylaxis or treatmen t of early postoperative infections should be further investigated.