The effect of sex, menstrual cycle phase and oral contraceptive use on intestinal permeability and ex-vivo monocyte TNFα release following treatment with lipopolysaccharide and hyperthermia

Tessa R Flood, Matthew R Kuennen, Sam D Blacker, Stephen D Myers, Ella F Walker, Ben J Lee

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    Abstract

    Investigate the impact of sex, menstrual cycle phase and oral contraceptive use on intestinal permeability and ex-vivo tumour necrosis factor alpha (TNFα) release following treatment with lipopolysaccharide (LPS) and hyperthermia. Twenty-seven participants (9 men, 9 eumenorrheic women (MC) and 9 women taking an oral contraceptive pill (OC)) completed three trials. Men were tested on 3 occasions over 6 weeks; MC during early-follicular, ovulation, and mid-luteal phases; OC during the pill and pill-free phase. Intestinal permeability was assessed following a 4-hour dual sugar absorption test (lactulose: rhamnose). Venous blood was collected each trial and stimulated with 100 μg·mL LPS before incubation at 37 °C and 40 °C and analysed for TNFα via ELISA. L:R ratio was higher in OC than MC (+0.003, p = 0.061) and men (+0.005, p = 0.007). Men had higher TNFα responses than both MC (+53 %, p = 0.004) and OC (+61 %, p = 0.003). TNFα release was greater at 40 °C than 37 °C (+23 %, p < 0.001). Men present with lower resting intestinal barrier permeability relative to women regardless of OC use and displayed greater monocyte TNFα release following whole blood treatment with LPS and hyperthermia. Oral contraceptive users had highest intestinal permeability however, neither permeability or TNFα release were impacted by the pill cycle. Although no statistical effect was seen in the menstrual cycle, intestinal permeability and TNFα release were more variable across the phases. 
    Original languageEnglish
    Article number155991
    Number of pages8
    JournalCytokine
    Volume158
    Early online date6 Aug 2022
    DOIs
    Publication statusPublished - Oct 2022

    Bibliographical note

    This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

    Keywords

    • Contraceptive
    • Inflammation
    • Gastrointestinal
    • Intestinal permeability
    • Cytokine
    • Menstrual cycle

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