Inhibition of intestinal macrophage chemotaxis to leukotriene B4 by sulphasalazine, olsalazine, and 5-aminosalicylic acid.
Purified intestinal macrophages obtained at resections for colonic neoplasms were investigated for chemotaxis to leukotriene B4 (LTB4) by the Millipore filter assay and leading front technique. Possible inhibition by drugs effective in the treatment of chronic inflammatory bowel disease (sulphasalazine, olsalazine, its active moiety 5-aminosalicylic acid (5-ASA), and the 5-ASA metabolite N-acetylated-5-ASA (ac-5-ASA)) was tested at therapeutic colonic concentrations of 0.01-10 mM. Leukotriene B4 at a dose of 10 nM was equipotent with casein (5 g litre-1) as regards chemoattraction of macrophages. Sulphasalazine, olsalazine and 5-ASA were potent inhibitors of macrophages chemotaxis to LTB4 with IC50 values of 0.43, 0.39 and 0.24 mM, respectively. These concentrations are below the lowest concentration of 5-ASA (2 mM) in the colonic lumen during conventional sulphasalazine treatment of patients with chronic inflammatory bowel disease. The inhibition of macrophage chemotaxis by these drugs may be important for this limitation of the local inflammatory process in chronic inflammatory bowel disease, and may in part explain the beneficial effect of systemic and local treatment with sulphasalazine. Leukotriene B4 appears to be an important inflammatory mediator for the activation of macrophages in colonic inflammation.
Nielsen
O H
OH
Department of Medical Gastroenterology, Herlev Hospital; University of Copenhagen, Denmark.
Verspaget
H W
HW
Elmgreen
J
J
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000636:Aminosalicylic Acids / Q000494:pharmacology*; D002633:Chemotaxis / Q000187:drug effects*; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D007413:Intestinal Mucosa / Q000166:cytology* / Q000187:drug effects; D007975:Leukotriene B4 / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D008264:Macrophages / Q000276:immunology*; D008297:Male; D019804:Mesalamine; D008875:Middle Aged; D012460:Sulfasalazine / Q000494:pharmacology*
D000636:Aminosalicylic Acids; D007975:Leukotriene B4; D012460:Sulfasalazine; D019804:Mesalamine; C032587:olsalazine