Inhibition of intestinal macrophage chemotaxis to leukotriene B4 by sulphasalazine, olsalazine, and 5-aminosalicylic acid

TY - JOUR

T1 - Inhibition of intestinal macrophage chemotaxis to leukotriene B4 by sulphasalazine, olsalazine, and 5-aminosalicylic acid

AU - Nielsen, O H

AU - Verspaget, H W

AU - Elmgreen, J

PY - 1988/6

Y1 - 1988/6

N2 - 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.

AB - 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.

KW - Adult

KW - Aged

KW - Aged, 80 and over

KW - Aminosalicylic Acids/pharmacology

KW - Chemotaxis/drug effects

KW - Female

KW - Humans

KW - In Vitro Techniques

KW - Intestinal Mucosa/cytology

KW - Leukotriene B4/antagonists & inhibitors

KW - Macrophages/immunology

KW - Male

KW - Mesalamine

KW - Middle Aged

KW - Sulfasalazine/pharmacology

M3 - Journal article

C2 - 2908754

SN - 0953-0673

VL - 2

SP - 203

EP - 211

JO - Alimentary Pharmacology and Therapeutics, Supplement

JF - Alimentary Pharmacology and Therapeutics, Supplement

IS - 3

ER -