Abstract # 1796 Impaired beta-adrenergic upregulation of anti-inflammatory cytokine production in patients with ulcerative colitis in remission

Abstract

Psychological factors, especially stress, demonstrably contribute to disease course in patients with inflammatory bowel diseases, but the underlying mechanisms remain unclear. Here, we tested whether neuroendocrine regulation of pro-/anti-inflammatory cytokine production by peripheral blood cells is altered in patients with ulcerative colitis in remission (UCR). Using a diluted-whole-blood stimulation assay, we measured the sensitivity of lipopolysaccharide-induced TNF-alpha and IL-10 production to dexamethasone (DEX; glucocorticoid agonist), terbutaline (TERB; beta2-adrenergic agonist), and GTS-21 (alpha7-nicotinic acetylcholine receptor agonist) in samples from UCR patients ( n = 26) and healthy controls ( n = 25). Additionally, we assessed anxiety and depression symptoms as well as chronic perceived stress and health-related quality-of-life with validated questionnaires (HADS, PSQ, IBDQ). Results showed that UCR patients exhibited greater anxiety, depression and chronic stress levels, and reduced quality-of-life. Plasma concentration of TNF-alpha was significantly higher and LPS-induced IL-10 production was significantly lower in UCR compared to HC. Independent of group, DEX and GTS-21 dose-dependently inhibited TNF-alpha and IL-10 production, whereas TERB inhibited TNF-alpha and upregulated IL-10 production. However, at higher TERB doses (i.e., stress levels), upregulation of IL-10 production was significantly diminished in UCR compared to HC, and impaired beta2-adrenergic IL-10 regulation correlated positively with the IBDQ systemic symptom score. These findings extend evidence of peripheral immune alterations in UC even during phases of remission, and support dysregulation of anti-inflammatory mechanisms that could play a role in stress-induced symptom exacerbation.