Elevated IL-6 and IL-22 in Early Pregnancy Are Associated with Worse Disease Course in Women with Inflammatory Bowel Disease

Richard Y Wu; Karren Xiao; Naomi Hotte; Parul Tandon; Yesmine Elloumi; Lindsy Ambrosio; Garett Dunsmore; Shokrollah Elahi; Karen I Kroeker; Levinus A Dieleman; Karen L Madsen; Vivian Huang

doi:10.3390/ijms231810281

Elevated IL-6 and IL-22 in Early Pregnancy Are Associated with Worse Disease Course in Women with Inflammatory Bowel Disease

Int J Mol Sci. 2022 Sep 7;23(18):10281. doi: 10.3390/ijms231810281.

Authors

Richard Y Wu^{1

2}, Karren Xiao², Naomi Hotte³, Parul Tandon², Yesmine Elloumi³, Lindsy Ambrosio³, Garett Dunsmore⁴, Shokrollah Elahi^{4

5

6

7}, Karen I Kroeker³, Levinus A Dieleman³, Karen L Madsen³, Vivian Huang^{2

3}

Affiliations

¹ Department of Medicine, University of Toronto, Toronto, ON M5T 2S8, Canada.
² Division of Gastroenterology and Hepatology, Mount Sinai Hospital, Toronto, ON M5T 2S8, Canada.
³ Division of Gastroenterology, University of Alberta, Edmonton, AB T6G 2R3, Canada.
⁴ Department of Medical Microbiology and Immunology, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, AB T6G 2R3, Canada.
⁵ Department of Dentistry, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, AB T6G 2R3, Canada.
⁶ Department of Oncology, University of Alberta, Edmonton, AB T6G 2R3, Canada.
⁷ Li Ka Shing Institute of Virology, University of Alberta, Edmonton, AB T6G 2R3, Canada.

Abstract

Inflammatory bowel diseases (IBD), including Ulcerative Colitis (UC) and Crohn’s disease (CD), are inflammatory conditions of the intestinal tract that affect women in their reproductive years. Pregnancy affects Th1- and Th2-cytokines, but how these changes occur during pregnancy in IBD is unclear. We performed a longitudinal profiling of serum cytokines in a cohort of 11 healthy pregnant women and 76 pregnant women with IBD from the first trimester of pregnancy to the first 12 months post-partum. Participants were monitored for biochemical disease activity (C-reactive protein [CRP] and fecal calprotectin [FCP]) and clinical activities. Maternal cytokines were measured using ELISA. We identified changes in Th1 and Th17 cytokines throughout pregnancy in healthy pregnant women. During pregnancy, maternal serum cytokine expressions were influenced by IBD, disease activity, and medications. Active UC was associated with an elevation in IL-21, whereas active CD was associated with elevated IFN-γ, IL-6, and IL-21. Interestingly, T1 serum cytokine levels of IL-22 (>0.624 pg/mL) and IL-6 (>0.648 pg/mL) were associated with worse IBD disease activity throughout pregnancy in women with UC and CD, respectively. This shows serum cytokines in pregnancy differ by IBD, disease activity, and medications. We show for the first time that T1 IL-22 and IL-6 correlate with IBD disease course throughout pregnancy.

Keywords: CD; IL-22; IL-6; UC; cytokines; pregnancy.

MeSH terms

C-Reactive Protein / metabolism
Colitis, Ulcerative*
Crohn Disease*
Cytokines / metabolism
Disease Progression
Female
Humans
Inflammatory Bowel Diseases*
Interleukin-22
Interleukin-6 / metabolism
Interleukins
Leukocyte L1 Antigen Complex
Pregnancy

Substances

Cytokines
Interleukin-6
Interleukins
Leukocyte L1 Antigen Complex
C-Reactive Protein

Grants and funding

The project is supported by local research support from CEGIIR, the University of Alberta Department of Medicine and Department of Gastroenterology, and the Mount Sinai Hospital Department of Medicine.