Does nicotine influence cytokine profile and subsequent cell cycling/apoptotic responses in inflammatory bowel disease?

Authors

  • Marian C. Aldhous PhD,

    Corresponding author
    1. Gastrointestinal Unit, School of Clinical and Molecular Medicine, University of Edinburgh, Western General Hospital, Edinburgh, Scotland, UK
    • Gastrointestinal Unit, 2nd Floor, Molecular Medicine Centre, University of Edinburgh, Western General Hospital, Edinburgh. EH4 2XU Scotland, UK
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  • Robin J. Prescott PhD,

    1. Medical Statistics Unit, School of Clinical Sciences and Community Health, University of Edinburgh, Western General Hospital, Edinburgh, Scotland, UK
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  • Simon Roberts MB BS,

    1. Gastrointestinal Unit, School of Clinical and Molecular Medicine, University of Edinburgh, Western General Hospital, Edinburgh, Scotland, UK
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  • Kay Samuel BSc (Hons),

    1. John Hughes Bennett Laboratory, Division of Oncology, University of Edinburgh, Western General Hospital, Edinburgh, Scotland, UK
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  • Martin Waterfall PhD,

    1. John Hughes Bennett Laboratory, Division of Oncology, University of Edinburgh, Western General Hospital, Edinburgh, Scotland, UK
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  • Jack Satsangi DPhil

    1. Gastrointestinal Unit, School of Clinical and Molecular Medicine, University of Edinburgh, Western General Hospital, Edinburgh, Scotland, UK
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Abstract

Background: Smoking differentially influences susceptibility to the inflammatory bowel diseases (IBDs) Crohn's disease (CD) and ulcerative colitis (UC). We investigated the effects of nicotine on cytokine, cell cycle, and apoptotic responses in peripheral blood mononuclear cells (PBMCs) from IBD patients and healthy controls (HCs).

Methods: PBMCs from IBD patients and HC were stimulated with lipopolysaccharide (LPS; 1 μg/mL) or phytohemagglutinin (PHA, 5 or 0.5 μg/mL), ± nicotine (1, 10, 100 μg/mL). Cytokines (IL1β, IL2, IL10, IL12/IL23p40, TGFβ, TNFα) were measured in supernatants at 24 hours. After 72 hours cells were analyzed by flow cytometry for cell cycle and apoptosis. Statistical modeling was used to identify interactions between cytokines and cell cycle / apoptosis and minimize confounding effects.

Results: Stimulation by LPS and PHA (5 μg/mL) increased IL12/IL23p40 production from CD and UC versus HC (P < 0.05); PHA (0.5 μg/mL) increased IL1β in UC and decreased TGFβ from CD and UC (P < 0.01). In all groups, nicotine reduced LPS- and PHA (0.5 μg/mL)-stimulated production of IL1β, IL10, TGFβ, and TNFα (P < 0.001). Cell cycle analysis showed that PHA, but not LPS, induced proliferation and decreased G0/G1 resting cells in CD and UC versus HC (P < 0.001). Nicotine decreased PHA-stimulated S-phase proliferation and increased G0/G1 resting cells (P < 0.01). Modeling showed independent associations between IL12/IL23p40 and apoptosis (P = 0.01), IL1β and resting cells (P = 0.006), TNFα and proliferating cells (P < 0.001). Disease activity and smoking habit had no effect.

Conclusions: Dysregulated cytokine profiles in UC and CD are associated with specific alterations in cell cycle responses; these effects may be modified by nicotine, and potentially by anticytokine therapies.

(Inflamm Bowel Dis 2008)

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