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BACKGROUND & AIMS: During severe pancreatitis, interleukin (IL)-1beta and tumor necrosis factor (TNF)-alpha are produced in large quantities. The aim of this study was to determine whether either one plays a more dominant role and if their detrimental effects are additive. METHODS: Necrotizing pancreatitis was induced in transgenic (-/-) knockout mice deficient in either IL-1 type 1 receptors, TNF type 1 receptors, or both IL-1 and TNF type 1 receptors. Wild-type mice served as controls. Mortality was assessed for 10 days. Additional animals were killed on days 0, 1, 2, 3, and 4 for determination of pancreatitis severity. RESULTS: All three knockout groups showed decreased amylase and lipase, histological score, serum IL-6, and mortality compared with wild-type groups. Animals devoid of receptors for both cytokines showed improved survival and decreased IL-6 levels compared with those devoid of either IL-1 or TNF receptors individually, yet they failed to show a further decrease in pancreatitis severity. CONCLUSIONS: Preventing the activity of IL-1beta or TNF-alpha has a nearly identical beneficial effect on the severity and mortality of acute pancreatitis. Preventing the activity of both cytokines concurrently has no additional effect on pancreatitis severity but further attenuates the systemic stress response and is associated with an additional but modest decrease in mortality. (Gastroenterology 1997 Nov;113(5):1741-6)

Background : Patients with irritable bowel syndrome (IBS) often suffer from multiple comorbid conditions, including: depression, anxiety, migraine, functional dyspepsia, fibromyalgia, and gynecologic disorders. These comorbidlties lead to a cycle whereby IBS and comorbid diseases worsen, with a negative impact on patients' productivity and quality of life (QoL). This prospective registry evaluated the effect of comorbid diseases on QoL and productivity of IBS patients. Method: Patients in primary care and GI specialist practices were evaluated by using Computer Assisted Telephone Interviews and chart review. The prevalence of nine key IBS-rsiatad comorbidities was collected: depression, anxiety, other psychiatric conditions, chronic pelvic pain, endometriosis, migraine, functional dyspepsia, fibromyalgia, and chronic fatigue syndrome. Baseline data on patients' QoL measured by the IBSQOL questionnaire, and lost workplace productivity and activity timp were collected. Patients were stratified into three groups (patients with no IBS-related comorbid conditions, patients with one comorbid condition, and patients with greater than one IBS-related comorbid condition). Results : Data were collected from a total of 1,426 IBS patients who reported 1,374 IBS-related comorbid conditions. Fifty percent of the patients (721) presented with one or more IBS-related comorbid conditions, the most prevalent conditions being depression (27%), anxiety (26%), migraine (15%), and functional dyspepsia (13%). Patients with IBS-related comorbidlties presented with an average of 1.90 comorbiditiee. A higher number of comorbidlties was associated with increasingly lower QoL scores in all nine dimensions (emotional, mental health, sleep, energy, physical functioning, eating habits, social role, main activity, and sexual relations). Patients with at least one comorbidity experienced a greater median productivity loss (3.5 vs. 2.1 days) and leisure time loss (11.2 vs. 6.4 days) in a 4-week period than patients without comorbid conditions. Comorbid conditions were equally prevalent in the newly diagnosed and established IBS patients. Conclusions : IBS patients often have multiple comorbid conditions. The presence of comorbid diseases leads to lower QoL status and larger lost productivity in IBS patients. Given their high disease burden, these patients may require special management.