Effect of the Interleukin 10 Polymorphisms on Interleukin 10 Production and Visceral Hypersensitivity in Chinese Patients with Diarrhea-Predominant Irritable Bowel Syndrome
Irritable bowel syndrome (IBS), a functional gastrointestinal disorder, is characterized by abdominal pain, bloating, and altered bowel habits. Among its subtypes, diarrhea-predominant IBS (IBS-D) is particularly associated with visceral hypersensitivity (VH), immune activation, and psychological disturbances. Previous studies have highlighted cytokine imbalances in IBS-D, particularly involving interleukin 10 (IL-10), an anti-inflammatory cytokine. This study investigated the impact of IL-10 genetic polymorphisms (rs1800871 and rs1800896) on IL-10 production and their correlation with clinical symptoms in Chinese patients with IBS-D, providing novel insights into the genetic and immunological basis of the disorder.
Study Design and Participant Recruitment
The study enrolled 120 IBS-D patients (diagnosed via Rome III criteria) and 144 healthy controls (HCs) from 2013 to 2018. Exclusion criteria included recent antibiotic/probiotic use, gastrointestinal or systemic diseases, infections, or prior abdominal surgery. Clinical evaluations included IBS symptom severity scores (IBS-SSS), Bristol stool scale, hospital anxiety and depression scale (HADS), and rectal distention tests for visceral sensitivity assessment. Colonoscopies and mucosal biopsies from the ileum and colon were performed to exclude organic diseases. Peripheral blood samples were collected for genetic and immunological analyses.
Genetic Analysis and IL-10 Polymorphisms
Two IL-10 polymorphisms, rs1800871 (A/G) and rs1800896 (T/C), located in the promoter region, were genotyped using SNaPshot technology. These SNPs were selected based on their potential influence on IL-10 production. Genotype distributions in HCs conformed to Hardy-Weinberg equilibrium (rs1800871: P = 0.540; rs1800896: P = 0.500). Detection rates exceeded 99.5% for both SNPs.
IL-10 Levels and Immunological Assays
IL-10 concentrations were measured in plasma, peripheral blood mononuclear cell (PBMC) culture supernatants, and ileal/colonic mucosal biopsies. Plasma and PBMC-derived IL-10 were quantified via ELISA, while mucosal expression was assessed via immunohistochemistry (IHC) using anti-IL-10 antibodies (1:800 dilution). PBMCs were isolated via Ficoll gradient centrifugation, cultured for 72 hours, and supernatants analyzed.
Key Findings
Genetic Susceptibility and Allele Frequencies
The rs1800896 C allele frequency was significantly lower in IBS-D patients (OR: 0.49, 95% CI: 0.27–0.92, P = 0.024), suggesting a protective role against IBS-D. In contrast, rs1800871 polymorphisms showed no significant association with disease risk. Under the dominant model (CC + CT vs. TT), rs1800896 variant carriers had reduced IBS-D risk (OR: 0.51, 95% CI: 0.27–0.99, P = 0.045).
IL-10 Production Across Genotypes
Subjects with the rs1800896 CT genotype exhibited higher plasma IL-10 levels compared to TT carriers (CT: 1.82 [1.29–3.22] pg/mL vs. TT: 1.37 [0.74–2.02] pg/mL, P = 0.003). Similarly, PBMC supernatants from CT carriers showed elevated IL-10 (55.87 [23.65–104.80] pg/mL vs. TT: 31.69 [12.09–76.87] pg/mL, P = 0.050). However, no genotype-dependent differences in mucosal IL-10 expression were observed.
Clinical Symptom Correlations
- Visceral Hypersensitivity: rs1800896 CT carriers exhibited higher pain thresholds during rectal distention (initial defecation: P = 0.007; defecation urgency: P = 0.010) than TT carriers, suggesting reduced VH.
- Psychological Factors: rs1800871 GG genotype carriers had higher HADS scores (indicating greater anxiety/depression) compared to AA/GA carriers (P = 0.023).
Mechanistic Insights
IL-10, produced by immune cells (T cells, monocytes, macrophages), suppresses proinflammatory cytokines like IL-6 and TNF-α. The rs1800896 C allele, linked to higher IL-10 production, may counteract systemic inflammation and visceral sensitivity in IBS-D. Reduced IL-10 levels in TT carriers could perpetuate immune dysregulation, lowering pain thresholds. Conversely, rs1800871 GG-associated psychological distress might reflect gut-brain axis dysregulation, where cytokine imbalances influence mood disorders.
Limitations and Implications
The study’s focus on two IL-10 polymorphisms limits exploration of other genetic contributors. Additionally, IL-10 measurements in mucosal tissues lacked genotype-specific differences, possibly due to localized regulatory mechanisms. Future research should expand to other SNPs and integrate transcriptional/epigenetic analyses. Clinically, identifying rs1800896 C allele carriers could stratify IBS-D patients for targeted anti-inflammatory therapies.
Conclusion
This study establishes a direct link between IL-10 rs1800896 polymorphisms, IL-10 production, and visceral hypersensitivity in Chinese IBS-D patients. The rs1800896 C allele’s protective role highlights IL-10’s therapeutic potential, while rs1800871 associations with psychological symptoms underscore the multifactorial nature of IBS-D. These findings advance understanding of IBS-D pathogenesis and pave the way for personalized treatment strategies.
doi.org/10.1097/CM9.0000000000000306
Was this helpful?
0 / 0