681 Differential Immune and Genetic Responses Mediate Suppression of Circular Smooth Muscle Contractility in Rat Models of Crohn's Colitis and Ulcerative Colitis

Abstract

G A A b st ra ct s patients 6 months after C. jejuni infection , 37 IBS-D patients and 19 IBS with constipation (IBS-C) provided stool and blood samples and underwent gut permeability measurement. Rectal mucosal biopsy mRNA was assessed by Affymatrix genechip and findings confirmed using TaqMan RT-PCR and correlated with histology, PBMC cytokine production, gut permeability and symptoms. RESULTS: Expression of the chemokines genes CCL11(eotaxin), CCL 13 (monocyte chemoattractant protein 4) and Calpain 8 were significantly increased in rectal biopsies 6 months after infection while NR1D1 & GPR161 were decreased (Table). Similar changes were seen in IBS-D and IBS-C. Gut permeability, mucosal mast cells and PMBC production of TNF-alpha & IL-6 were significantly elevated 6 months following infection. Individuals with persistent bowel dysfunction had higher mast cell numbers. There were no other differences in mucosal mRNA nor PBMC cytokine production from those who recovered completely, though they were more likely to have rectal bleeding. PI-BD patient were also more likely to be female, younger and have significantly higher PHQ12, anxiety and depression scores than PI-non-IBS. Overall PBMC TNF, IL-10 and IL-1-beta production correlated closely (r= 0.8 0.90) but none correlated with gut permeability. TNF showed a weak correlation with days per week with loose stool, r=0.24, p<0.05. Eosinophils counts did not differ between groups but did correlate with bowel frequency in IBS-D (r=0.5, p=0.02, n=21) . CONCLUSION: Mucosal expression of proinflammatory chemokines genes, mast cell numbers and PBMC cytokine production are elevated 6 months following C. jejuni infection. Similar increased chemokine mRNA and PCMC cytokine production are also seen in IBS patients regardless of subtype. Gene expression as assessed by TaqMan Real-Time PCR