Antisecretory factor expression is regulated by inflammatory mediators and influences the severity of experimental autoimmune encephalomyelitis.
Antisecretory factor (ASF) was originally identified as a potent inhibitor of intestinal fluid secretion induced by a number of enterotoxins. In addition to its involvement in intestinal fluid secretion, ASF modulates the proliferation of memory/effector T cells and is expressed by cells of the immune system. This report describes the role of ASF in modulating immune responses and assesses the regulation of ASF during an in vivo immunological reaction. ASF expression was redistributed during adoptively transferred experimental autoimmune encephalomyelitis (EAE), and in response to other inflammatory stimuli. Administration of the anti-ASF antibody TLD-1A8A increased the clinical severity and duration of the disease. Consistent with these findings, addition of TLD-1A8A to T cell proliferation assays resulted in up-regulation of the proinflammatory cytokines IL-18 and IL-6 and in down-regulation of IL-10. Furthermore, we identified cytokines that regulated the expression of ASF at both the mRNA and protein level. ASF, therefore, appears to play a previously unappreciated and potentially important role in the regulation of immune responses.
Department of Pathology, Dartmouth Medical School--DHMC Lebanon, NH 03756, USA.
Todd S
TS
Davidson
William F
WF
Hickey
D019264:Adoptive Transfer; D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D000930:Antidiarrheals / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects; D002490:Central Nervous System / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D005786:Gene Expression Regulation; D007371:Interferon-gamma / Q000494:pharmacology; D016753:Interleukin-10 / Q000378:metabolism; D020382:Interleukin-18 / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D009479:Neuropeptides / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D011917:Rats, Inbred Lew; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D014018:Tissue Distribution
D000911:Antibodies, Monoclonal; D000930:Antidiarrheals; D020382:Interleukin-18; D015850:Interleukin-6; D008070:Lipopolysaccharides; D009479:Neuropeptides; C049628:antisecretory factor; D016753:Interleukin-10; D007371:Interferon-gamma