ArticleInflammation research : official journal of the European Histamine Research Society ... [et al.]2026
Docosahexaenoic acid supplementation inhibits monocyte exhaustion memory formation during sepsis.
Article in Inflammation research : official journal of the European Histamine Research Society ... [et al.], 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
OBJECTIVE AND
designDocosahexaenoic acid (DHA) is an omega-3 fatty acid with important roles in inflammation resolution. We tested the impact of DHA supplementation on monocyte exhaustion, an immune memory state contributing to chronic inflammation and immunosuppression following sepsis. MATERIALS OR SUBJECTS: Ex vivo sepsis modeling was performed with C57BL/6 mouse bone marrow monocytes (BMMCs) and peripheral blood mononuclear cells (PBMCs) from septic patients. TREATMENT: BMMCs stimulated with lipopolysaccharide (100 ng/mL) for 5 days were supplemented with 60 µM DHA. Septic patient PBMCs were treated for 24 h with 0, 15, 30, 45, or 60 µM DHA.
methodsMonocyte exhaustion was assayed by flow cytometry, qRT-PCR, and cytometric arrays. DNA methylation changes linked to exhaustion memory were measured by bisulfite pyrosequencing. Western blots were performed to link DHA treatment to altered cell signaling pathways in septic monocytes.
resultsDHA supplementation suppresses the expression major exhaustion regulators CD38 and PD-L1 and dampens inflammatory cytokine transcription. These effects were mechanistically linked to STAT1/3 inhibition and accompanied by altered DNA methylation at immune regulators. DHA treatment also reduced CD157 cell surface levels and CCL2 secretion, both contributors to tissue invasion and injury during sepsis.
conclusionsOur results support the therapeutic application of DHA for the prevention of chronic immune dysfunction in sepsis survivors.
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