**5. Inflammation limiting strategies**

## **5.1 Inflammation limiting strategies in organ donors**

The use of methylprednisolone, alone or as part of hormonal replacement, reduces the immunological activation observed after brain death in terms of decreasing cytokine production and preventing alterations induced by proinflammatory mediators [36, 42]. In a prospective randomized study, reduced serum and graft cytokine expression and improved graft function in human liver transplantation was found/reported after methylprednisolone administration [42]. Inflammation in the heart and kidneys is also reduced. The reduction in cytokine activation is almost comparable to the levels seen in living donor transplantation [36]. Methylprednisolone use is associated with increased organ retrieval and improved short- and long-term outcome for most transplanted organs [12].

Numerous other agents and approaches are currently under investigation as part of organ protection and preservation strategies.

Among such strategies, active removal of cytokines by haemoadsorption was shown to be feasible, leading to at least a moderate fall in cytokine concentration in circulation, attenuating the inflammatory response associated with brain death [9].

Although no RCTs in humans currently exist, animal models have also demonstrated a reduced inflammatory response and improved oxygenation when using noradrenaline [43, 44].

Since glucagon-like peptide-1 (GLP1) analogues were shown to possess interesting cytoprotective effects in different liver and pancreatic disease models, these molecules were also tested in experimental transplantation models. Treatment with the GLP1 analogue exendin-4 (Ex-4) relieved brain dead-induced liver [45], renal [46] and pancreatic islet injury [47] through alleviation of inflammation and oxidative stress.

After single administration of antithymocyte globulin (ATG) to brain-dead mice, the inflammatory reaction in the myocardium showed a significant reduction in IL-2 expression and the reduction of IL-6 deposition in media cells in ATGtreated specimens compared to controls [48].

Targeting complement activation after the induction of brain death also reduced renal inflammation and improved renal function before transplantation in animal models [49]. Recently, a study by Jager et al. [50]. has shown that experimental
