Insulin inhibits IL-6 production in the kidneys in brain-dead pigs

Introduction

Kidneys transplanted from brain dead donors have a poorer function and a higher risk of rejection than kidneys from living donors [1]. This might partly be due to the inflammatory changes in the kidneys after brain death [2]. In a previous porcine study we found that a high-insulinaemic-euglucaemic clamp modulated the renal cytokine response to lipopolysaccharide infusion towards anti-inflammation [3]. We hypothesized that insulin in brain death would give a similar cytokine response, and tested this hypothesis in brain-dead pigs by studying the effect of insulin on renal IL-6 content.

Methods

In 16 anaesthetized and mechanically ventilated pigs (38–42 kg bw) brain death was induced by inflation of an epidurally placed balloon catheter. Eight pigs received insulin at a constant rate (0.6 mU/kg/min). Blood glucose was clamped at 4.5 mmol/l by infusion of 20% glucose. The kidneys were removed 6 hours after brain death and biopsies from the renal cortex and medulla were taken for measurements of IL-6, by ELISA (pg/mg total protein) and of IL-6 mRNA by PCR (optimal density ratio IL-6/ HRPT).

Results

See Table 1. In the renal medulla IL-6 and IL-6 mRNA were lower in the treated group, whereas in the cortex only IL-6 was lower.

Table 1 (abstract P250)

Conclusion

Insulin inhibits renal IL-6 production in brain-dead pigs. This indicates that insulin treatment of organ donors might be beneficial for kidney graft survival after transplantation.