ArticleFrontiers in immunology2022
Inhibition of human macrophage activation
Article in Frontiers in immunology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
21 citing papers in PubMed, 30 citations in OpenAlex.
- Effects of estrogen and progesterone on neuroactive steroids and cytokines in patients with suicidality.Psychoneuroendocrinology · 2023Trial
- Neurosteroid (3α,5α)3-hydroxypregnan-20-one enhancement of anti-inflammatory chemokine CX3CL1 exhibits sex, brain region, and cellular specificity in alcohol-preferring rats.Psychopharmacology · 2026Article
- Brexanolone infusion produces sustained anti-inflammatory and neurotrophic effects in patients with postpartum depression that predict symptom improvement.Translational psychiatry · 2026Article
- Sex differences in immune cells: mechanistic perspectives and clinical correlates in physiology and disease.Frontiers in immunology · 2026Review
- Impact of testosterone-based gender-affirming hormone therapy on toll-like receptor transcript levels and peripheral blood leukocyte counts in transmasculine individuals.Frontiers in immunology · 2026Observational
- Neuroactive steroid exposure impacts neurodevelopment: Comparison of human and rodent placental contribution.Journal of neuroendocrinology · 2025Review
- New directions in neurosteroid therapeutics in neuropsychiatry.Neuroscience and biobehavioral reviews · 2025Review
- Structural modifications to pregnane neurosteroids alter inhibition of LPS/Lipid A binding at the MD-2 activation site within the TLR4 signaling complex.Frontiers in immunology · 2025Article
- Novel Inhibitory Actions of Neuroactive Steroid [3α,5α]-3-Hydroxypregnan-20-One on Toll-like Receptor 4-Dependent Neuroimmune Signaling.Biomolecules · 2024Article
- Current Developments in the Treatment of Postpartum Depression: Zuranolone.The Eurasian journal of medicine · 2024Article
- Neurosteroids in Glioma: A Novel Therapeutic Concept.Life (Basel, Switzerland) · 2024Review
- Neurosteroid [3α,5α]-3-Hydroxy-pregnan-20-one Enhances the CX3CL1-CX3CR1 Pathway in the Brain of Alcohol-Preferring Rats with Sex-Specificity.Life (Basel, Switzerland) · 2024Article
- Neuroactive Steroids, Toll-like Receptors, and Neuroimmune Regulation: Insights into Their Impact on Neuropsychiatric Disorders.Life (Basel, Switzerland) · 2024Review
- Article
- Novel neurosteroid therapeutics for post-partum depression: perspectives on clinical trials, program development, active research, and future directions.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2024Review
- Neuroimmune Mechanisms of Opioid Use Disorder and Recovery: Translatability to Human Studies, and Future Research Directions.Neuroscience · 2023Review
- Deleterious Interaction between the Neurosteroid (3α,5α)3-Hydroxypregnan-20-One (3α,5α-THP) and the Mu-Opioid System Activation during Forced Swim Stress in Rats.Biomolecules · 2023Article
- Article
- Neurosteroid [3α,5α]-3-hydroxy-pregnan-20-one enhances IL-10 production via endosomal TRIF-dependent TLR4 signaling pathway.Frontiers in endocrinology · 2023Article
- Research Trends and Hot Spots of Allopregnanolone Research in the Last 20 Years: A Bibliometric Analysis.Drug design, development and therapy · 2023Review
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
Abstract
We recently discovered that (3α,5α)3-hydroxypregnan-20-one (allopregnanolone) inhibits pro-inflammatory toll-like receptor (TLR) activation and cytokine/chemokine production in mouse macrophage RAW264.7 cells. The present studies evaluate neurosteroid actions upon TLR activation in human macrophages from male and female healthy donors. Buffy coat leukocytes were obtained from donors at the New York Blood Center (http://nybloodcenter.org/), and peripheral blood mononuclear cells were isolated and cultured to achieve macrophage differentiation. TLR4 and TLR7 were activated by lipopolysaccharide (LPS) or imiquimod in the presence/absence of allopregnanolone or related neurosteroids and pro-inflammatory markers were detected by ELISA or western blotting. Cultured human monocyte-derived-macrophages exhibited typical morphology, a mixed immune profile of both inflammatory and anti-inflammatory markers, with no sex difference at baseline. Allopregnanolone inhibited TLR4 activation in male and female donors, preventing LPS-induced elevations of TNF-α, MCP-1, pCREB and pSTAT1. In contrast, 3α,5α-THDOC and SGE-516 inhibited the TLR4 pathway activation in female, but not male donors. Allopregnanolone completely inhibited TLR7 activation by imiquimod, blocking IL-1-β, IL-6, pSTAT1 and pIRF7 elevations in females only. 3α,5α-THDOC and SGE-516 partially inhibited TLR7 activation, only in female donors. The results indicate that allopregnanolone inhibits TLR4 and TLR7 activation in cultured human macrophages resulting in diminished cytokine/chemokine production. Allopregnanolone inhibition of TLR4 activation was found in males and females, but inhibition of TLR7 signals exhibited specificity for female donors. 3α,5α-THDOC and SGE-516 inhibited TLR4 and TLR7 pathways only in females. These studies demonstrate anti-inflammatory effects of allopregnanolone in human macrophages for the first time and suggest that inhibition of pro-inflammatory cytokines/chemokines may contribute to its therapeutic actions.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.