5-Aminosalicylic acid is a potent inhibitor of interleukin 1 beta production in organ culture of colonic biopsy specimens from patients with inflammatory bowel disease.

Abstract

Interleukin 113 in biopsy specimens from inflamed colonic mucosa of patients with active inflammatory bowel disease was studied. Compared with normal colonic mucosal biopsy specimens, a significantly greater amount of interleukin ,13 was present in rectal mucosa before (median (range) 4*3 (2-0-11.8) v 119-2 (30.1-286.8) pg/mg; p<001) and produced during organ culture (39.1 (9.4-106-8) Interleukin 1 has been shown to be a mediator of a number of inflammatory and immunological responses." The precise mechanisms leading to inflammation in inflammatory bowel disease remain to be determined, however, and the mode of action of the therapeutically active drug 5-aminosalicylic acid is not clear. There are good reasons to believe that interleukin may be implicated in the pathogenesis of inflammatory bowel disease.' Its functional properties include T lymphocyte activation,4 enhanced antibody synthesis by B lymphocytes,5 and increased fibroblast proliferation.6 It induces adhesion molecules on endothelial cells which facilitate migration of polymorphonuclear leucocytes and mononuclear cells to sites of inflammation.7 It is also an endogenous pyrogen and induces synthesis of acute phase proteins by hepatocytes.2Enhanced production of interleukin 113 by mononuclear cells isolated from colonic mucosa with active inflammatory bowel disease has been shown.8 In the present study, we investigated whether the therapeutically active drug 5-aminosalicylic acid could inhibit interleukin 113 production by biopsy specimens from inflamed colons, and compared it with sulphapyridine (the therapeutically inactive moiety of sulphasalazine) and dexamethasone, whose effects on interleukin ,13 synthesis by monocytes have previously been characterised.9 We also evaluated the relation of interleukin 13 and thromboxane B2 and studied the effect of 5-aminosalicylic acid on basal synthesis of eicosanoids. Methods PATIENTSTwenty four patients with active ulcerative colitis (14 women, six men; median age 48 5 years (range 20-79)), two with active Crohn's disease (both women, aged 20 and 32 years), and 12 patients with normal colons (five women, seven men; median age 52 5 (range 27-81)) were studied. Biopsy specimens were obtained while these patients were undergoing colonoscopy for clinical reasons. The control group with normal colonic mucosa (confirmed on routine histology) were patients who were undergoing investigations for gastrointestinal symptoms and in whom no abnormality of the gastrointestinal tract was found.Eight patients with inflammatory bowel disease were being treated with sulphasalazine, seven with mesalazine, six with oral prednisolone, four with steroid enemas, and four with azathioprme.

Lactobacillus paracasei and Lactobacillus plantarum strains downregulate proinflammatory genes in an ex vivo system of cultured human colonic mucosa

“…In general, some evidence obtained by intervention or observational studies needs to be supported by the description of their mechanism of action and the discovery of biomarkers, in order to comply with the regulations of governmental and supranational organizations, as occurs in Japan . During the past twenty years, cultured intestinal fragments from patients suffering inflammatory bowel disease (IBD) were used to determine their cytokine profile or the effects of several drugs, through the detection of inflammatory mediators (Borruel et al 2002;Mahida et al 1991), yet transcriptomic studies on cultured intestinal explants are scarce. Here, our main aim was to determine whether strains of the genus Lactobacillus could attenuate inflammatory processes in a colon organ culture model.…”

Molecular basis of the potential of mesalazine to prevent colorectal cancer

“…Indeed, it is well known that mesalazine can modulate various inflammatory pathways (e.g. production of inflammatory cytokines, activity of inducible nitric oxide synthase, activation of nuclear factor-κB) that are relevant to CRC initiation and progression [13][14][15][16] . There is also evidence that mesalazine inhibits the formation of reactive oxygen species (ROS) from polymorphonuclear leukocytes [17] , which leads to a decrease or complete inhibition of DNA damage, a phenomenon that has been involved in colon carcinogenesis.…”

Update on the role of modified release mesalamine in the management of ulcerative colitis and Crohn&rsquo;s disease

“…5-ASA drugs appear to impair binding of interferon-gamma (IFN-γ) to its receptor 9 and disrupt the action of this key pro-inflammatory chemokine, 10 including blocking of its detrimental effects on gut barrier function. 11 5-ASA agents reduce ex vivo production of interleukin-1 beta (IL-1β) in IBD mucosal biopsies 12,13 and by circulating peripheral blood monocytes 14 and also appear to impair the production of interleukin 2 (IL-2) with consequent effects on proliferation of T-lymphocytes. 15 In addition to their effects on key cytokines, alterations in other key mediators of inflammation have also been described.…”