Decreased corticosensitivity in quiescent Crohn's disease - An ex-vivo study using whole blood cell cultures

Corticosensitivity influences the degree and the duration of an inflammator y reaction by altering target cell responses to endogenous and/or exogenous glucocorticoids. Indeed, different clinical responses to glucocorticoids h ave been observed among patients with Crohn's disease, suggesting different degrees of corticosensitivity in these subjects. The purpose of this study was to compare the corticosensitivity of patients with quiescent Crohn's d isease to that of healthy subjects (HS). Nineteen patients with quiescent C rohn's disease and 14 HS were studied; all patients were steroid-free for a t least six months; 7 of the 19 were corticosteroid-dependent (CSD) and tre ated with nonglucocorticoid immunosuppressants at the time of the study. Co rticosensitivity was measured by the inhibition of LPS-induced cytokine sec retion in whole blood cell cultures treated with increasing concentrations (10(-9) to 10(-6) M) of dexamethasone. Tumor-necrosis factor-alpha (TNF-alp ha), interleukin-6 (IL-6), and interleukin-1 beta (IL-1 beta) were measured using specific immunoassays, Crohn's disease patients had a markedly decre ased dexamethasone-mediated inhibition of TNF-alpha (P < 0.01), IL-6 (P < 0 .001), and IL-1 beta (P < 0.01) compared to healthy subjects, with a shift of the dexamethasone dose-response curve to the right. No significant diffe rences in the basal and LPS-stimulated secretion of the three cytokines wer e observed between CSD and non-CSD patients, and both subgroups of patients had similar degrees of dexamethasone-mediated cytokine inhibition. We conc lude that patients with Crohn's disease have a significant decrease in the corticosensitivity of their leukocytes, This may be related to a specific g enetic/constitutional background and/or could be acquired, due to inflammat ion-related endocrine and/or immune factors.