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Insulin inhibits IL-6 production in the kidneys in brain-dead pigs
Critical Care volume 10, Article number: P250 (2006)
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.
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.
References
Terasaki PI, Cecka JM, Gjertson DW, Takemoto S: High survival rates of kidney transplants from spousal and living unrelated donors. N Engl J Med 1995, 333: 333-336. 10.1056/NEJM199508103330601
Skrabal CA, Thompson LO, Potapov EV, et al.: Organ-specific regulation of pro-inflammatory molecules in heart, lung, and kidney following brain death. J Surg Res 2005, 123: 118-125. 10.1016/j.jss.2004.07.245
Brix-Christensen V, Andersen SK, Andersen R, et al.: Acute hyperinsulinemia restrains endotoxin-induced systemic inflammatory response: an experimental study in a porcine model. Anesthesiology 2004, 100: 861-870. 10.1097/00000542-200404000-00016
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Barklin, A., Larsson, A., Schmitz, O. et al. Insulin inhibits IL-6 production in the kidneys in brain-dead pigs. Crit Care 10 (Suppl 1), P250 (2006). https://doi.org/10.1186/cc4597
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DOI: https://doi.org/10.1186/cc4597