Sex-dependent bioactive lipid mediator profiles in multiple sclerosis.

Authors

Wing Hee Fung, Serhii Chornyi, Menno M Schoonheim, Bernard Mj Uitdehaag, Joep Killestein, Eva Mm Strijbis, Gijs Kooij

Published in

Multiple sclerosis journal - experimental, translational and clinical. Volume 12. Issue 3. Pages 20552173261475501. Epub Aug 08, 2026.

Abstract

Pathophysiological drivers of sex differences in multiple sclerosis (MS) remain unclear. Potential candidates include bioactive lipid mediators (LMs), which are pivotal regulators of neuro-inflammatory responses.
To investigate sex-dependent LM differences in MS.
Plasma lipids were measured using targeted HPLC-MS/MS in a birth-year MS cohort (N = 410; n = 285 MS, n = 169 RRMS, n = 80 SPMS and n = 36 PPMS). Lipid profiles were compared between sexes and correlated with disability (Expanded Disability Status Scale (EDSS)), neuroaxonal damage (neurofilament light, NfL), whole brain volume (WBV) and T2 lesion volume (LV).
In healthy controls, 9-HOTrE levels were higher in women than men. In individuals with MS, women had higher 9-HOTrE, 18-HEPE and 9-HODE levels than men, while men had higher 15-HEPE, 17-HDHA and 11,12-DiHET levels than women. Among these LMs, increased 11,12-DiHET levels were associated with higher EDSS and NfL levels, while higher levels of the remaining LMs, such as 9-HOTrE, were associated with lower EDSS and lower LV.
These findings provide insights into potential sex-dependent lipid-mediated pathophysiological mechanisms in MS patients. Our findings suggest that certain LMs, such as 9-HOTrE, may display neuroprotective effects in MS.

PMID:
42572568
Bibliographic data and abstract were imported from PubMed on 10 Aug 2026.

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