The logistic regression analysis has indicated that low expression levels of IL-2 and IL-10, together with higher ASCA IgG titers were independently associated with penetrating/stricturing CD.
The IL2-rs6822844 polymorphism modified CD predisposition (P=0.002; odds ratio, OR (95% confidence interval, CI)=0.61 (0.44-0.84)); this was replicated in the other Spanish cohort, resulting in a strong protective effect of the minor allele in the merged samples (P=0.0002; OR (95% CI)=0.70 (0.58-0.85)).
We confirm previously reported disease related pathways and provide evidence for IL-2 Receptor Beta Chain in T cell Activation and IL-9 signaling as Crohn's disease associated pathways.
The STAT5 gene is known to influence colonic permeability, mucosal regeneration, and interleukin 2 production, although its role in the distribution of Crohn's disease is unclear.
Chronic intestinal lesions of patients with Crohn's disease (CD) are associated with a T helper (Th) 1-type cytokine profile, including high levels of interleukin 2 (IL-2) and interferon gamma (IFN-gamma).
A sensitive reverse haemolytic plaque assay to detect lymphokine-secreting T cells, and Northern blot analysis to detect expression of lymphokine messenger RNA (mRNA) were used to study interferon-gamma (IFN-gamma) and interleukin-2 (IL-2) production in the mucosa of children with Crohn's disease or ulcerative colitis (UC), and in histologically normal mucosa from patients without inflammatory bowel disease.
Accordingly, proliferative responses of LPL-T in patients with Crohn's disease and ulcerative colitis to stimulation with CD3 MoAb plus IL-2 were examined and compared with controls.
Interrogation of pathways from eight pathway databases yields strong support for enriched pathways, indicating links between Crohn's disease (CD) and cytokine-driven networks that modulate immune responses; between rheumatoid arthritis (RA) and "Measles" pathway genes involved in immune responses triggered by measles infection; and between type 1 diabetes (T1D) and IL2-mediated signaling genes.
Twenty-nine subjects (16 CD and 13 UC) and 45 healthy controls were enrolled in this study and had plasma samples tested for ASCA and cytokines (IL-2, IL-4, IL-6, IL-10, IFN-γ, TNF-α), besides clinical evaluation.
In contrast, only ulcerative colitis cell isolates but not biopsies contained significantly reduced concentrations of IL-2 mRNA compared to those of control and Crohn's disease samples, and no correlation was found between cell and biopsy contents.