Impact of sepsis-associated cytokine storm on plasma NGAL during acute kidney injury in a model of polymicrobial sepsis

organ dysfunction during sepsis [1]. One promising biomarker for its early detection is neutrophil gelatinaseassociated lipocalin (NGAL) [2,3]. During sepsis, cytokines, including TNFα, IL6 and IL10, initiate a broad variety of signalling that aff ect AKI development. Using a lipo polysaccharide-induced AKI animal model, correlation of NGAL expression to TNFα but not IL6 expression was previously described [4]. During polymicrobial sepsis, it remains unclear whether there is a correlation between protein levels and the role of plasma NGAL as an infl am matory protein rather than a marker of AKI. After gaining permission (Thueringer Landesamt fuer Lebensmittelsicherheit und Verbraucherschutz; TVA02-10/10), sepsis in mice was induced by injection of human faeces. Mice were sacrifi ced at baseline, 6 h and 24 h post-sepsis insult. Plasma NGAL, cytokines, blood urea nitrogen (BUN), serum creatinine (Crea) and other laboratory markers were ascertained and ANOVA and Spearman correlation testing performed. Sepsis symptoms developed within the fi rst 6 h (Table 1). During sepsis, IL6, IL10, monocyte chemotactic protein-1 (MCP1), interferon-gamma (IFNγ) and TNFα signifi cantly increased (Figure 1a). Concerning sepsisassociated AKI, plasma NGA L was already elevated at 6 h, whereas Crea and BUN remained stable (Figure 1b). After 24 h, these markers were increased as well. Although Crea was still normal at 6 h, there was a signifi cant positive correlation with NGAL, which was maintained at 24 h (Table 2). A signifi cant correlation between NGAL and TNFα was observed at 6 h and 24 h. In addition, signifi cant correlations of NGAL with IL6, IL10 and MCP1 were found exclusively after 24 h but not after 6 h. No correlation was detected for IFNγ. Data indicate that the early increase of plasma NGAL during sepsis is not solely a result of infl ammation and its associated cytokine storm but rather results from early kidney damage. As described recently [4], the association of TNFα with NGAL could be confi rmed during polymicrobial sepsis. Since cytokines stimulate the expression of each other, it might be assumed that the late association of NGAL with IL6, IL10 and MCP1 was triggered by TNFα. We hypothesize that septic AKI, as remote organ failure, is mainly initiated by TNFα. Th is might