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Updated: Sep 25, 2025
Author Spotlight: Developing Innovative Therapeutic Strategies for Hemorrhagic Shock Research
Published on: March 22, 2024
Inhibition of Macrophage Migration Inhibitory Factor Activity Attenuates Haemorrhagic Shock-Induced Multiple Organ
Nikita M Patel1, Noriaki Yamada1,2, Filipe R M B Oliveira3
1William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, United Kingdom.
Objective:
The 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.
Background:
The 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.
Methods:
The 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.
Results:
We 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.
Conclusion:
Our 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.
Insights
Macrophage migration inhibitory factor (MIF) is elevated in trauma patients and contributes to organ dysfunction after hemorrhagic shock (HS). Inhibiting MIF with ISO-1 reduces organ injury and inflammation, suggesting MIF inhibitors as a potential therapy for trauma-induced multiple organ dysfunction syndrome (MODS).
Area of Science:
- Immunology
- Trauma Pathophysiology
- Inflammation Research
Background:
- Multiple organ dysfunction syndrome (MODS) following trauma leads to high mortality.
- Macrophage migration inhibitory factor (MIF) is a cytokine involved in inflammatory responses, but its role in trauma remains unclear.
- Understanding MIF's role is crucial for developing effective treatments for trauma-induced complications.
Purpose of the Study:
- To measure macrophage migration inhibitory factor (MIF) levels in polytrauma patients and rats post-hemorrhagic shock (HS).
- To evaluate the efficacy of the MIF inhibitor ISO-1 in mitigating MODS in HS rat models.
- To determine if ISO-1 treatment impacts NF-κB and NLRP3 pathway activation in response to HS.
Main Methods:
- ELISA was used to quantify MIF levels in patient plasma and rat serum.
- Acute HS rat models were established to assess the effects of ISO-1 on MODS.
- Western blot analysis was performed on kidney and liver tissues to examine NF-κB and NLRP3 activation.
Main Results:
- MIF levels were significantly increased in polytrauma patients and rats subjected to HS.
- HS induced organ injury, dysfunction, and hypotension in rats.
- ISO-1 treatment attenuated organ injury and dysfunction in HS rat models.
- ISO-1 administration reduced the activation of NF-κB and NLRP3 pathways in the kidneys and liver.
Conclusions:
- MIF plays a significant role in the pathophysiology of trauma- and hemorrhage-induced organ injury.
- MIF inhibitors, such as ISO-1, show therapeutic potential for managing MODS.
- Targeting MIF could be a promising strategy for improving outcomes in patients suffering from trauma and hemorrhage.
