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P055 Brain-Immune Axis Regulation is Responsive to Cognitive Behavioral and Mindfulness-Based Stress Reduction in Crohn’s Disease

Nemirovsky, A.(1);Ilan, K.(2);Lerner, L.(2);Cohen-Lavi , L.(3);Schwartz, D.(4);Goren, G.(5);Sergienko, R.(5);Greenberg, D.(6);Slonim-Nevo , V.(7);Sarid, O.(7);Friger, M.(5);Regev, S.(7);Odes, S..(8);Hertz, T.(9);Monsonego, A.(10);

(1)Faculty of Health Sciences- Ben-Gurion University of the Negev, The Shraga Segal Department of Microbiology- Immunology- and Genetics-, Beer Sheva, Israel;(2)Faculty of Health Sciences- Ben-Gurion University of the Negev, The Shraga Segal Department of Microbiology- Immunology- and Genetics, Beer Sheva, Israel;(3)Faculty of Health Sciences- Ben-Gurion University of the Negev- and Vaccine and Infectious Disease Division- Fred Hutch Cancer Research Center- Seattle- WA- USA, The Shraga Segal Department of Microbiology- Immunology- and Genetics, Beer Sheva, Israel;(4)Faculty of Health Sciences- Ben-Gurion University of the Negev, Gastroenterology & Hepatology, Beer Sheva, Israel;(5)Faculty of Health Sciences- Ben-Gurion University of the Negev, Department of Public Health, Beer Sheva, Israel;(6)Faculty of Health Sciences- Ben-Gurion University of the Negev, Department of Health Systems Management- School of Public Health- Guilford Glazer Faculty of Business and Management, Beer Sheva, Israel;(7)Ben-Gurion University of the Negev, Spitzer Department of Social Work, Beer Sheva, Israel;(8)Faculty of Health Sciences- Ben-Gurion University of the Negev, Gastroenterology & Hepatology, Metar, Israel;(9)Ben-Gurion University of the Negev, The Shraga Segal Department of Microbiology- Immunology- and Genetics- Faculty of Health Sciences- and Vaccine and Infectious Disease Division- Fred Hutch Cancer Research Center- Seattle- WA- USA, Beer Sheva, Israel;(10)Ben-Gurion University of the Negev, The Shraga Segal Department of Microbiology- Immunology- and Genetics- Faculty of Health Sciences- and The National Institute of Biotechnology in the Negev, Beer Sheva, Israel

Background

Crohn's disease (CD) is a chronic inflammatory bowel disease associated with psychological stress that is regulated primarily by the pituitary-hypophysis-adrenal (HPA) axis. Here, we determined whether the psychological characteristics of CD patients associate with their inflammatory state, and whether a 3-month period of Cognitive Behavioral and Mindfulness-Based Stress Reduction (COBMINDEX) impacts their inflammatory process.

Methods

Circulating inflammatory markers (IFN-α, IFN-γ, TNF-α, MCP-1, IL-6, IL-8, IL-10, IL-12p70, IL-18, IL-23, and IL-33) and a wide range of psychological parameters were measured before (T1) and after (T2) COBMINDEX in CD patients. Inflammatory parameters were also compared to age- and sex-matched healthy controls (HCs) at T1, and to wait-list CD patients (at T1 and T2) who were followed for 3 months but did not receive COMBINDEX. Psychological symptoms were assessed by two questionnaires: the Perceived Stress Scale PSS4, and the Brief Symptom Inventory of psychological distress with Global Severity Index GSI. Statistical significance was assessed using Spearman correlation.

Results

CD patients (N=100, mean age 33.6 ± 13 years, 69% female, Harvey-Bradshaw Index mean 31± 55) exhibited increased peripheral low-grade inflammation compared with HCs, demonstrated by higher serum levels of interleukin (IL)-6 (mean 4.084± 8.4) and IL-18 (mean 302.09± 286) shown in Figure 1. Notably, IL-18 levels correlated with a higher stress score and a lower wellbeing score in CD patients (Figure 2). COBMINDEX was accompanied by changes in inflammatory markers that coincided with changes in cortisol: changes in serum levels of cortisol correlated positively with those of IL-10 (0.32, p<0.05) and INFα (0.36, p<0.05) and correlated negatively with those of MCP-1 (-0.34, p<0.05). Finally, baseline inflammatory markers of CD patients predicted COBMINDEX efficacy, as changes in HBI were negatively correlated with cytokines levels of IFNa (p=0.046), IFNg (p=0.03), IL-10 (p=0.002), IL-23 (p=0.025), IL33 (p=0.009) and IL12p70 (p=0.037) at T1 in the COBMINDEX group, but not in the wait-list group. In addition, basal levels of circulating cortisol at T1 negatively correlated with changes in GSI (-0.33, p<0.05) between T1 and T2 in the COBMINDEX group, but not in the wait-list group.

Conclusion

Our results show that CD patients have a characteristic immunological profile that correlates with psychological stress and disease activity, and predicts COBMINDEX outcomes. We suggest that COBMINDEX induces stress resilience in CD patients, which not only impacts their well-being, but also their disease-associated inflammatory process.

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