Human Crohn’s disease (CD) is usually characterized by a relapsing and remitting course (flare-ups followed by clinical remission) in the early phases of the disease. Cigarette smoking is the best known environmental risk factor for CD. We studied the influence of four weeks cigarette smoke exposure on the disease course of TNBS-induced murine colitis, modeling distal active Crohn-like colitis.
Methods & Results
10 mice were exposed to the tobacco smoke of five cigarettes four times a day with 30 min. smoke-free intervals, five days per week for four weeks, after which colitis was induced by intrarectal TNBS treatment. At day two and three post-colitis induction, mice were sacrificed.
We observed a strong induction of histologic inflammation by TNBS after two days, but not anymore after three days. In addition, we demonstrated an increase of Kc, Cxcl-2, Il-1β, Ccl19 and Ccr6 in smoke-exposed TNBS-challenged mice after two days. Cxcl-2 increased both at two and three days post-TNBS-enema. Kc, Il-1β, Ccl19 and Ccr6 increased only after two days post-TNBS-enema.
Discussion
Here, we show an altered histology of TNBS colitis after four weeks of CS exposure. We found a further induction of Cxcl2 and Il-1β mRNA and protein due to smoke exposure, suggesting increased neutrophil attraction and increased macrophage activity in the inflamed distal colon. We speculate that CS boosts inflammation in the initiation phase towards an IBD-like flare-up. Knowledge of the molecular targets of smoke exposure might pave the way for adaptation of current treatment strategies in IBD patients.