Serum macrophage migration inhibitory factor levels predict brain atrophy in people with primary progressive multiple sclerosis

Background: Macrophage migration inhibitory factor (MIF) is a cytokine linked to multiple sclerosis (MS) progression that is thought to be inhibited by ibudilast. SPRINT-MS was a phase 2 placebo-controlled trial of ibudilast in progressive multiple sclerosis (PMS).

Objective: To determine whether baseline MIF levels predict imaging outcomes and assess the effects of ibudilast on serum and cerebrospinal fluid (CSF) MIF levels in people with PMS treated with ibudilast.

Methods: Participants in the SPRINT-MS trial were treated with either ibudilast or placebo and underwent brain magnetic resonance imaging (MRI) every 24 weeks over a duration of 96 weeks. MIF was measured in serum and CSF.

Results: MIF levels were compared with imaging outcomes in 223 participants from the SPRINT-MS study. In the primary progressive multiple sclerosis (PPMS) cohort, males had higher serum (p < 0.001) and CSF (p = 0.01) MIF levels, as compared with females. Higher baseline serum MIF levels in PPMS were associated with faster brain atrophy (beta = -0.113%, 95% confidence interval (CI): -0.204% to -0.021%; p = 0.016). These findings were not observed in secondary progressive multiple sclerosis (SPMS). Ibudilast did not affect either serum or CSF MIF levels.

Conclusions: Serum MIF levels were associated with male sex and predicted brain atrophy in PPMS, but not SPMS. Ibudilast did not demonstrate an effect on MIF levels, as compared with placebo, although we cannot exclude a functional effect.

 

Comments:

It seems like the study delved into the role of macrophage migration inhibitory factor (MIF) in progressive multiple sclerosis (PMS) and the effects of ibudilast, a potential inhibitor of MIF, on patients. The study found interesting correlations between baseline MIF levels, sex differences, and disease progression in different forms of PMS.

1. **Baseline MIF Levels & Sex Differences:**
   - In primary progressive MS (PPMS), males had higher serum and cerebrospinal fluid (CSF) MIF levels compared to females.
   - Higher baseline serum MIF levels in PPMS were associated with faster brain atrophy.

2. **Disease Progression Correlation:**
   - This association between higher serum MIF levels and brain atrophy was observed in PPMS but not in secondary progressive MS (SPMS).

3. **Ibudilast Effects:**
   - Ibudilast treatment didn't impact serum or CSF MIF levels significantly compared to the placebo group. However, the study couldn't rule out a potential functional effect of ibudilast on MIF.

This study suggests that MIF might have different roles in different subtypes of progressive MS and could be correlated with disease progression, particularly in PPMS. While ibudilast didn't seem to influence MIF levels significantly, its functional impact on MIF warrants further investigation.

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