Author:
Patel Nikita M.,Yamada Noriaki,Oliveira Filipe R. M. B.,Stiehler Lara,Zechendorf Elisabeth,Hinkelmann Daniel,Kraemer Sandra,Stoppe Christian,Collino Massimo,Collotta Debora,Alves Gustavo Ferreira,Ramos Hanna Pillmann,Sordi Regina,Marzi Ingo,Relja Borna,Marx Gernot,Martin Lukas,Thiemermann Christoph
Abstract
ObjectiveThe aim of this study was to investigate (a) macrophage migration inhibitory factor (MIF) levels in polytrauma patients and rats after haemorrhagic shock (HS), (b) the potential of the MIF inhibitor ISO-1 to reduce multiple organ dysfunction syndrome (MODS) in acute (short-term and long-term follow-up) HS rat models and (c) whether treatment with ISO-1 attenuates NF-κB and NLRP3 activation in HS.BackgroundThe MODS caused by an excessive systemic inflammatory response following trauma is associated with a high morbidity and mortality. MIF is a pleiotropic cytokine which can modulate the inflammatory response, however, its role in trauma is unknown.MethodsThe MIF levels in plasma of polytrauma patients and serum of rats with HS were measured by ELISA. Acute HS rat models were performed to determine the influence of ISO-1 on MODS. The activation of NF-κB and NLRP3 pathways were analysed by western blot in the kidney and liver.ResultsWe demonstrated that (a) MIF levels are increased in polytrauma patients on arrival to the emergency room and in rats after HS, (b) HS caused organ injury and/or dysfunction and hypotension (post-resuscitation) in rats, while (c) treatment of HS-rats with ISO-1 attenuated the organ injury and dysfunction in acute HS models and (d) reduced the activation of NF-κB and NLRP3 pathways in the kidney and liver.ConclusionOur results point to a role of MIF in the pathophysiology of trauma-induced organ injury and dysfunction and indicate that MIF inhibitors may be used as a potential therapeutic approach for MODS after trauma and/or haemorrhage.
Funder
William Harvey Research Foundation
Conselho Nacional de Desenvolvimento Científico e Tecnológico
Deutsche Forschungsgemeinschaft
Subject
Immunology,Immunology and Allergy
Cited by
3 articles.
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