Interleukin-9 release from human kidney grafts and its potential protective role in renal ischemia/reperfusion injury

Objective and design The pathophysiology of ischemia/ reperfusion (I/R) injury is dominated by an inflammatory response. In the identification of new therapeutic agents, the role of individual cytokines may be essential. Interleukin (IL)-9 is a pleiotropic cytokine recently identified to be involved in various immune responses. In this study, the role of IL-9 in renal I/R injury was assessed. Methods We performed repeated direct measurements of arteriovenous IL-9 concentration differences over the reperfused graft in human kidney transplantation. Results Substantial renal IL-9 release was observed from deceased donor kidneys (P = 0.006). In contrast, living donor kidneys, which have a more favourable clinical outcome, did not release IL-9 during early reperfusion (P = 0.78). Tissue expression of IL-9 did not change upon reperfusion in both living and deceased human donor kidneys. To assess the role of IL-9 in I/R injury, an experimental study comprising IL-9 inhibition in mice undergoing renal I/R was performed. Although there was no difference in kidney function, structural damage was significantly aggravated in anti-IL-9 treated mice. Conclusions Deceased donor grafts show a substantial IL-9 release upon reperfusion in clinical kidney transplantation. However, inhibition of IL-9 aggravated kidney damage, suggesting a regulating or minor role of IL-9 in clinical I/R injury.