Seyed Mohammad Piri, Zahra Ghodsi, Sina Shool, Ali Anjomshoa, Amir Azarhomayoun, Ehsan Jangholi, Hamid Reza Dehghan, Rasha Atlasi, Alexander R. Vaccaro, Vafa Rahimi-Movaghar

June 2021, Volume 30, Issue 6, pp 1474 - 1494 Review Article Read Full Article 10.1007/s00586-021-06718-2

First Online: 24 January 2021

Macrophage migration inhibitory factor as a therapeutic target after traumatic spinal cord injury: a systematic review


Macrophages play an important role in mediating damage after Spinal cord injury (SCI) by secreting macrophage migration inhibitory factor (MMIF) as a secondary injury mediator. We aimed to systematically review the role of MMIF as a therapeutic target after traumatic SCI.


Our systematic review has been performed according to the PRISMA 2009 Checklist. A systematic search in the scientific databases was carried out for studies published before 20 February 2019 from major databases. Two researchers independently screened titles. The risk of bias of eligible articles was assessed, and data were extracted. Finally, we systematically analyzed and interpreted related data.


785 papers were selected for the title and abstract screening. 12 papers were included for data extraction. Eight animal studies were of high quality and the remaining two were of medium quality. One of the two human studies was of poor quality and the other was of fair quality. MMIF as a pro-inflammatory mediator can cause increased susceptibility to glutamate-related neurotoxicity, increased nitrite production, increased ERK activation, and increased COX2/PGE2 signaling pathway activation and subsequent stimulation of CCL5-related chemotaxis. Two human studies and six animal studies demonstrated that MMIF level increases after SCI. MMIF inhibition might be a potential therapeutic target in SCI by multiple different mechanisms (6/12 studies).


Most animal studies demonstrate significant neurologic improvement after administration of MMIF inhibitors, but these inhibitors have not been studied in humans yet. Further clinical trials are need to further understand MMIF inhibitor utility in acute or chronic SCI.

Level of Evidence I

Diagnostic: individual cross-sectional studies with the consistently applied reference standard and blinding.

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