1. ¹Department of Nephrology and Medical Intensive Care, Charité-Universitätsmedizin Berlin, Campus Virchow-Klinikum, Berlin, Germany
2. ²Department of Pathophysiology, Pozna University of Medical Sciences, Pozna, Poland
3. ³Department of Nephrology, Pozna University of Medical Sciences, Pozna, Poland

Correspondence: Professor A Jörres, MD, Department of Nephrology and Medical Intensive Care, Charité-Universitätsmedizin Berlin, Campus Virchow-Klinikum, Augustenburger Platz 1, Berlin D-13353, Germany. E-mail: achim.joerres@charite.de

Received 19 June 2008; Revised 17 November 2008; Accepted 22 November 2008; Published online 2 February 2009.

Abstract

Polymorphonuclear leukocyte (PMN) infiltration is a cardinal feature of peritonitis. CXC chemokine ligands 1 and 8 (CXCL1 and CXCL8), and the cytokine granulocyte colony-stimulating factor (G-CSF) are the key mediators of PMN accumulation. Increasing evidence points to an important role of human peritoneal fibroblasts (HPFB) in the response of the peritoneum to infection. We have examined the synthesis of PMN-targeting cytokines by HPFB exposed to intraperitoneal milieu as represented by peritoneal dialysate effluent (PDE) from patients undergoing peritoneal dialysis. PDE obtained during peritonitis, but not during infection-free periods, significantly increased production of CXCL1, CXCL8, and G-CSF by HPFB. The effect was largely blocked by antibodies to interleukin-1 (IL-1), whereas neutralization of tumor necrosis factor- (TNF) had no major effect. Similar pattern of inhibition was observed when HPFB were exposed to conditioned media from endotoxin-stimulated peritoneal macrophages. Significance of IL-1 stimulation was further shown in experiments with recombinant cytokines. Compared with TNF, exposure of HPFB to recombinant IL-1 resulted in a much higher release of PMN-targeting cytokines. The assessment of mRNA degradation revealed that the IL-1-induced transcripts of CXCL1, CXCL8, and G-CSF were more stable compared with those induced by TNF. These data indicate that HPFB can be a significant source of PMN-targeting cytokines when stimulated with IL-1 in the inflamed peritoneum.