Why choose this post to discuss.
It’s all about migration inhibiton factor.
Why is this interesting
Ibudilast is a molecule that blocks phospodiesterase 4 and inhibits progressive MS. Rolipram also blocks phosphodiesterase 4 and maybe makes relapsing MS worse. What’s the difference. One thing ibudilast does is that it blocks migration inhibiton factor…..which inhibits macrophage migration.
Is this the link?
Hjæresen S, Sejbaek T, Axelsson M, Mortensen SK, Vinsløv-Jensen H, Pihl-Jensen G, Novakova L, Pedersen CB, Halle B, Poulsen FR, Zhang M, Benedikz E, Frederiksen JL, Lycke J, Illes Z, Fex-Svenningsen Å.J MIF in the cerebrospinal fluid is decreased during relapsing-remitting while increased in secondary progressive multiple sclerosis. Neurol Sci. 2022;439:120320. doi: 10.1016/j.jns.2022.120320.
Background: Macrophage migration inhibitory factor (MIF) is involved in the function of both the innate and adaptive immune systems and in neuroprotection and has recently been implicated in multiple sclerosis (MS).
Objectives: Determination of MIF levels in the cerebrospinal fluid (CSF) of patients with distinct subtypes of MS and the cellular localization of MIF in human brain tissue.
Methods: The levels of MIF were investigated in CSF from patients with clinically isolated syndrome (CIS) (n = 26), relapsing-remitting MS (RRMS) (n = 22), secondary progressive MS (SPMS) (n = 19), and healthy controls (HCs) (n = 24), using ELISA. The effect of disease-modifying therapies in the RRMS and SPMS cohorts were examined. Cellular distribution of MIF in the human brain was studied using immunochemistry and the newly available OligoInternode database.
Results: MIF was significantly decreased in treatment-naïve CIS and RRMS patients compared to HCs but was elevated in SPMS. Interestingly, MIF levels were sex-dependent and significantly higher in women with CIS and RRMS. MIF expression in the human brain was localized to neurons, astrocytes, pericytes, and oligo5 oligodendrocytes but not in microglia.
Conclusion: The finding that MIF was decreased in newly diagnosed CIS and RRMS patients but was high in patients with SPMS may suggest that MIF levels in CSF are regulated by local MIF receptor expression that affects the overall MIF signaling in the brain and may represent a protective mechanism that eventually fails.