ArticleThe Journal of clinical investigation2017
Androgen-mediated sex bias impairs efficiency of leukotriene biosynthesis inhibitors in males.
Article in The Journal of clinical investigation, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers, 1 of them a synthesis that pooled it.
What it found
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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
55 citing papers in PubMed, 1 synthesis or guideline pooled it, 91 citations in OpenAlex.
- Sex Differences in Exercise-Induced Bronchoconstriction in Athletes: A Systematic Review and Meta-Analysis.International journal of environmental research and public health · 2020Pooled it
- Reorganization of Innate Immune Cell Lipid Profiles by Bioinspired Meroterpenoids to Limit Inflammation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Platelet-macrophage cooperation drives IL-33-dependent type 2 lung immunopathology in a sex-biased manner.The Journal of allergy and clinical immunology · 2026Article
- Diagnostic Role of Aspirin Challenge in NSAID-Exacerbated Respiratory Disease: A Prospective Single-Center Study in China.Allergy, asthma & immunology research · 2026Article
- Mast cell-specific CysLT2 receptor signaling inhibits cysteinyl leukotriene-dependent mast cell activation and type 2 allergic lung inflammation.Cell reports · 2026Article
- Sex, hormones, and lung health.Physiological reviews · 2026Review
- Sex Differences in Oxidative Stress Concerning Allergic Diseases.Biomolecules · 2025Review
- Glycosaminoglycans in osteoarthritis cartilage promote inflammation by preferential activation of the lipoxygenase rather than the cyclooxygenase pathway.Advances in rheumatology (London, England) · 2025Article
- Cysteinyl Leukotrienes in Allergic Inflammation.Annual review of pathology · 2025Review
- Sex hormone deprivation abolishes sex-specific differences in murine colon inflammation and related lipid mediator production.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2024Article
- Downregulation of HNF4A enables transcriptomic reprogramming during the hepatic acute-phase response.Communications biology · 2024Article
- PEG-Lipid-PLGA Hybrid Particles for Targeted Delivery of Anti-Inflammatory Drugs.Pharmaceutics · 2024Article
- Article
- Glucocorticoids regulate lipid mediator networks by reciprocal modulation of 15-lipoxygenase isoforms affecting inflammation resolution.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- The Role of Sex Differences in Bone Health and Healing.Biology · 2023Review
- Association between Sex-RelatedJournal of clinical medicine · 2023Article
- Theophylline-Induced Relaxation Is Enhanced after Testosterone Treatment via Increased KInternational journal of molecular sciences · 2023Article
- Anti-Inflammatory Activities ofPlants (Basel, Switzerland) · 2023Article
- Updates on immune mechanisms in aspirin-exacerbated respiratory disease.The Journal of allergy and clinical immunology · 2023Review
- Allosteric Activation of 15-Lipoxygenase-1 by Boswellic Acid Induces the Lipid Mediator Class Switch to Promote Resolution of Inflammation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Article
Corrections and comments
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Authors and funding
18 authors at 6 institutions in 5 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Proinflammatory leukotrienes (LTs) are produced by 5-lipoxygenase (5-LO) aided by 5-LO-activating protein (FLAP). LT biosynthesis inhibitors are currently under clinical investigation as treatments for respiratory and cardiovascular diseases. Here, we have revealed a sex bias in the efficiency of clinically relevant LT biosynthesis inhibitors, showing that their effects are superior in females. We found that androgens cause these sex differences by impeding the LT-biosynthetic 5-LO/FLAP complex assembly. Lower doses of the FLAP inhibitor MK886 were required to reduce LTB4 levels in exudates of female versus male mice and rats. Following platelet-activating factor-induced shock, MK886 increased survival exclusively in female mice, and this effect was abolished by testosterone administration. FLAP inhibitors and the novel-type 5-LO inhibitors licofelone and sulindac sulfide exhibited higher potencies in human blood from females, and bioactive 5-LO/FLAP complexes were formed in female, but not male, human and murine leukocytes. Supplementation of female blood or leukocytes with 5α-dihydrotestosterone abolished the observed sex differences. Our data suggest that females may benefit from anti-LT therapy to a greater extent than males, prompting consideration of sex issues in LT modifier development.
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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.