Circulating resistin levels are early and significantly increased in deceased brain dead organ donors, correlate with inflammatory cytokine response and remain unaffected by steroid treatment

Abstract

Introduction: Resistin is a pro-inflammatory adipokine that increases after brain injury (trauma, bleeding) and may initiate an inflammatory response. Resistin was found increased in deceased, brain dead organ donors (DBD) and correlated with delayed graft function after kidney transplantation. The kinetics of resistin during brain death (BD), its impact on the inflammatory response and the influence of several donor variables on resistin levels are still unknown.

Methods: Resistin along with a panel of Th1/Th2 cytokines [interferon (IFN)-gamma, interleukin (IL)-1beta, IL-2, IL-6, IL-8, IL10, IL-12, IL-13 and tumor necrosis factor (TNF)] was analyzed in 36 DBDs after the diagnosis of BD and before organ procurement and in 12 living kidney donors (LD). The cytokine levels and resistin were analyzed in relation to donor parameters including cause of death, donors' age and steroid treatment.

Results: Resistin levels were higher in DBDs both at BD diagnosis and before organ procurement compared to LD (p < 0.001). DBDs had significantly increased IL-1beta, IL-6, IL-8, IL-10 and TNF levels at both time points compared with LD. In DBDs, resistin at BD diagnosis correlated positively with IL-1beta (rs 0.468, p = 0.007), IL-6 (rs 0.511, p = 0.002), IL-10 (rs 0.372, p = 0.028), IL-12 (rs 0.398, p = 0.024), IL-13 (rs 0.397, p = 0.030) and TNF (rs 0.427, p = 0.011) at procurement. The cause of death, age over 60 and steroid treatment during BD did not affect resistin levels. However, steroid treatment significantly decreased pro-inflammatory cytokines IL-1beta, IL-8, TNF and IFN-gamma at the time of organ procurement.

Conclusions: Resistin is increased early in DBDs, remains increased throughout the period of BD and correlates strongly with pro-inflammatory mediators. Resistin level, in contrast to cytokines, is not affected by steroid treatment. Resistin increase is related to the BD but is not influenced by age or cause of death. Resistin may be one of the initial triggers for the systemic inflammatory activation seen in DBDs.

Figure 1

a Resistin levels in all the DBD donors at the time of the diagnosis of brain death (T1), immediately before organ procurement (T2) and in living kidney donors (LD). b Resistin levels at both timepoints in DBD donors divided according to the cause of death. The box plots show medians and interquartile range, whiskers show 5–95th percentiles; ^#p < 0.001; CVA cerebrovascular accident.

Figure 2

The Th1 cytokines in all the brain dead donors at the time of the diagnosis of brain death (T1) and immediately before organ procurement (T2) and in living kidney donors (LD). The box plots on logarithmic scale show medians and interquartile range (IQR), whiskers show 2.5–97.5th percentiles. *p < 0.05; **p < 0.01, ***p < 0.001.

Figure 3

The Th2 cytokines in all the brain dead donors at the time of the diagnosis of brain death (T1) and immediately before organ procurement (T2) and in living kidney donors (LD). The box plots on logarithmic scale show medians and interquartile range (IQR), whiskers show 2.5–97.5th percentiles. *p < 0.05; ***p < 0.001.

Figure 4

The effect of steroid treatment of the brain dead donors on several cytokines at the time of the diagnosis of brain death (T1) and immediately before organ procurement (T2). The box plots show medians and interquartile range (IQR), whiskers show 2.5–97.5th percentiles. Grey boxes denote treated DBD donors whereas open boxes represent untreated DBD donors. *p < 0.05; **p < 0.01, ***p < 0.001.

Figure 5

The effect of steroid treatment of the brain dead donors on interleukin-6 at the time of the diagnosis of brain death (T1) and immediately before organ procurement (T2). The box plots on logarithmic scale show medians and interquartile range (IQR), whiskers show 2.5–97.5th percentiles. Grey boxes denote treated DBD donors whereas open boxes represent untreated DBD donors. *p < 0.05; **p < 0.01, ***p < 0.001.