Cytokines and platelet-activating factor in human inflamed colonic mucosa.
Colonic biopsy specimens from patients with active ulcerative colitis and controls were incubated for four hours in the presence or absence of calcium ionophore or antihuman immunoglobulin E (IgE). Platelet-activating factor (PAF) was determined in the tissue by aggregation assay after extraction with 80% ethanol. PAF was not detected in normal mucosa, whereas A23187 and antihuman IgE stimulated its activity: mean +/- SE, 43.2 +/- 8.6 and 33.0 +/- 6.1 pg/10 mg wet weight, respectively. In active ulcerative colitis, A23187 and antihuman IgE induced significantly higher stimulation of PAF synthesis compared to their effects on normal mucosa. The enhanced stimulation of PAF induced by A23187 was dose-dependently inhibited by sulphasalazine, 5-aminosalicylic acid and prednisolone, but not by sulfapyridine. Colonic interleukin-1 content and release during 24 h of culture were significantly higher in patients with active ulcerative colitis and Crohn's disease compared to normal subjects. Prednisolone significantly and dose-dependently inhibited interleukin-1 release. These results suggest that colonic generation of PAF and interleukin-1 are elevated in patients with inflammatory bowel disease and, thus, may have a role in its pathogenesis. Pharmacological suppression of colonic PAF and interleukin-1 production may have beneficial therapeutic effects.
Department of Medicine, Hadassah University Hospital, Jerusalem, Israel.
D
D
Rachmilewitz
R
R
Eliakim
P
P
Simon
M
M
Ligumsky
F
F
Karmeli
D000636:Aminosalicylic Acids / Q000494:pharmacology; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D000888:Antibodies, Anti-Idiotypic / Q000276:immunology; D000001:Calcimycin / Q000494:pharmacology; D003093:Colitis, Ulcerative / Q000188:drug therapy / Q000378:metabolism*; D003106:Colon / Q000187:drug effects / Q000378:metabolism*; D003424:Crohn Disease / Q000188:drug therapy / Q000378:metabolism*; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D007073:Immunoglobulin E / Q000276:immunology; D007375:Interleukin-1 / Q000096:biosynthesis*; D007413:Intestinal Mucosa / Q000187:drug effects / Q000378:metabolism*; D019804:Mesalamine; D009924:Organ Culture Techniques; D010972:Platelet Activating Factor / Q000096:biosynthesis*; D011239:Prednisolone / Q000494:pharmacology; D012460:Sulfasalazine / Q000494:pharmacology; D013844:Thiazoles / Q000494:pharmacology
D000636:Aminosalicylic Acids; D000894:Anti-Inflammatory Agents, Non-Steroidal; D000888:Antibodies, Anti-Idiotypic; D007093:Imidazoles; D007375:Interleukin-1; D010972:Platelet Activating Factor; D013844:Thiazoles; D007073:Immunoglobulin E; D000001:Calcimycin; D012460:Sulfasalazine; D019804:Mesalamine; D011239:Prednisolone; C052026:6-(4-fluorophenyl)-2,3-dihydro-5-(4-pyridinyl)imidazo(2,1-b)thiazole