Enhanced mucosal cytokine production in inflammatory bowel disease.
Proliferation, maturation, chemotaxis, and activation of neutrophils and monocytes are mediated largely by cytokines, including colony-stimulating factors and lymphokines. Cytokines produced in the intestinal mucosa contribute to the increased migration of neutrophils and monocytes into the lesion of inflammatory bowel disease and to the activation of these inflammatory cells. Lamina propria mononuclear cells isolated from colon tissue from 14 patients with inflammatory bowel disease (IBD) and from histologically normal controls were studied. Cells from IBD-affected tissue produced significantly more colony-stimulating factor activity (1402 +/- 252 U) per 2 x 10(6) cells than those from normal mucosa (362 +/- 85 U), mainly because of the increased production of granulocyte colony-stimulating factor and interleukin 1. This was accompanied by increases in the amount of specific messenger RNA for these two cytokines in lamina propria mononuclear cells from mucosa of patients with Crohn's disease (CD) compared with normal controls. By contrast, there was a substantial reduction in interleukin 3 production in CD and in ulcerative colitis lamina propria mononuclear cells, and this was reflected in significantly reduced expression of interleukin 3 messenger RNA in CD cells. Of the agents used in the therapy of IBD, hydrocortisone and 5-aminosalicylic acid, but not cyclosporin A, markedly suppressed in vitro production of cytokines by lamina propria mononuclear cells, suggesting that their therapeutic efficacy in vivo may be due in part to down-regulation of cytokine production in the inflamed mucosa.
Division of Clinical Sciences, John Curtin School of Medical Research, Australian National University, Canberra.
W E
WE
Pullman
S
S
Elsbury
M
M
Kobayashi
A J
AJ
Hapel
W F
WF
Doe
D000636:Aminosalicylic Acids / Q000494:pharmacology; D016572:Cyclosporine / Q000494:pharmacology; D005455:Fluorescent Antibody Technique; D016179:Granulocyte Colony-Stimulating Factor / Q000096:biosynthesis; D006133:Growth Substances / Q000096:biosynthesis* / Q000235:genetics; D006801:Humans; D006854:Hydrocortisone / Q000494:pharmacology; D015212:Inflammatory Bowel Diseases / Q000378:metabolism*; D007378:Interleukins / Q000096:biosynthesis; D007413:Intestinal Mucosa / Q000166:cytology / Q000378:metabolism*; D019804:Mesalamine; D009504:Neutrophils / Q000502:physiology; D015347:RNA Probes; D012333:RNA, Messenger / Q000032:analysis
D000636:Aminosalicylic Acids; D006133:Growth Substances; D007378:Interleukins; D015347:RNA Probes; D012333:RNA, Messenger; D016179:Granulocyte Colony-Stimulating Factor; D019804:Mesalamine; D016572:Cyclosporine; D006854:Hydrocortisone