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Inhibition of intestinal macrophage chemotaxis to leukotriene B 4 by sulphasalazine, olsalazine, and 5‐aminosalicylic acid
Author(s) -
NIELSEN O. H.,
VERSPAGET H. W.,
ELMGREEN J.
Publication year - 1988
Publication title -
alimentary pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.308
H-Index - 177
eISSN - 1365-2036
pISSN - 0269-2813
DOI - 10.1111/j.1365-2036.1988.tb00689.x
Subject(s) - leukotriene b4 , aminosalicylic acid , medicine , leukotriene , chemotaxis , inflammatory bowel disease , pharmacology , macrophage , metabolite , immunology , inflammation , leukotriene c4 , chemistry , in vitro , biochemistry , receptor , disease , asthma
SUMMARY Purified intestinal macrophages obtained at resections for colonic neoplasms were investigated for chemotaxis to leukotriene B 4 (LTB 4 ) 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 m m . Leukotriene B 4 at a dose of 10 n m 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 LTB 4 with IC 50 values of 0.43, 0.39 and 0.24 m m , respectively. These concentrations are below the lowest concentration of 5—ASA (2 m m ) 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 B 4 appears to be an important inflammatory mediator for the activation of macrophages in colonic inflammation.