Time-course of plasma inflammatory mediators in a rat model of brain death

•The long observation of a small animal model with maintained circulation following BD induction•The first measurement of time-dependent changes in plasma IL-13, TIMP-1, and CXCL3 concentrations after BD•The increase in immune response, particularly pro-inflammatory responses, after BD is time-dependent.•High levels of CXCL3 in the transplanted organ can be mediated by chemotaxis of T cells to sites of rejection.

BackgroundBrain death (BD) is a donor-associated risk factor that negatively affects transplantation outcome. The inflammation associated with BD appears to have a negative effect on organ quality. Complement activation, apoptosis, and pro-inflammatory cytokine and chemokine expression are significantly increased after BD. To better understand this process, we investigated plasma chemokine and cytokine levels for 8 h after BD in a rodent model.MethodsThirteen healthy adult male Sprague Dawley rats were intubated and mechanically ventilated. After induction of BD, animals were kept hemodynamically stable for 8 h. A panel of immune response factors, including cytokines and chemokines, were measured immediately prior to the induction of BD and at 1, 4, and 8 h after BD by multiplex analyses in 10 rats.ResultsIn the early phase of BD, we observed an increase in heart rate and a decrease in mean arterial pressure. Only limited fluctuations were noted in the partial pressure of O2, O2 saturation, and HCO3. Monocyte-/macrophage- and lymphocyte-derived mediators (IL-2, IL-4, and IFN-γ) increased steadily during the 8-hour monitoring period.ConclusionsThe increase in immune responses, particularly pro-inflammatory responses, after BD is time-dependent. Cytokines and chemokines from donors and recipients require further investigation to determine the optimal time frames for organ transplantation in rodent models and humans.