Mucosal tolerance to KLH reduces BSA-induced arthritis in rats--an indication of bystander suppression.
Mucosal tolerance has been shown to reduce disease severity in animal models mimicking human autoimmune diseases. The objective of this study was to examine whether mucosal tolerance against keyhole limpet haemocyanin (KLH) could be used to reduce bovine serum albumin (BSA)-induced arthritis in rats and whether anti-inflammatory drugs or passive cigarette smoke affected tolerance induction. Arthritis was induced by immunizing rats with BSA and then injecting BSA into one knee and saline into the other knee for comparison. Prior to BSA immunization, the rats were treated intranasally with KLH or saline and KLH then injected in the knee joints at the time of BSA injection, or the rats were treated with or without anti-inflammatory drugs or subjected to cigarette smoke prior to and during intranasal treatment with BSA. The rats that received intranasal treatment with KLH had a significantly less inflammation in their left knee joint compared to rats that received intranasal saline treatment. Beclamethasone increased the tolerance effect of BSA, whereas passive cigarette smoke abrogated the mucosal tolerance. This data suggests that bystander suppression can be used to treat arthritis and other autoimmune diseases, even when the autoantigen is not known.
Freysdottir
Jona
J
Lyfjathroun hf-Biopharmaceuticals, Reykjavik, Iceland. jonaf@landpitali.is
Hardardottir
Ingibjorg
I
Gizurarson
Sveinbjorn
S
Vikingsson
Arnor
A
D000818:Animals; D001168:Arthritis / Q000139:chemically induced / Q000188:drug therapy / Q000276:immunology* / Q000473:pathology*; D001507:Beclomethasone / Q000627:therapeutic use; D024201:Bystander Effect / Q000187:drug effects / Q000276:immunology*; D002417:Cattle; D049109:Cell Proliferation / Q000187:drug effects; D005260:Female; D006433:Hemocyanins / Q000276:immunology*; D007108:Immune Tolerance / Q000187:drug effects / Q000276:immunology*; D018928:Immunity, Mucosal / Q000187:drug effects / Q000276:immunology; D007371:Interferon-gamma / Q000378:metabolism; D016753:Interleukin-10 / Q000378:metabolism; D051381:Rats; D018124:Receptors, Tumor Necrosis Factor / Q000378:metabolism; D012710:Serum Albumin, Bovine / Q000276:immunology* / Q000633:toxicity; D013154:Spleen / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D014028:Tobacco Smoke Pollution / Q000009:adverse effects
D018124:Receptors, Tumor Necrosis Factor; D014028:Tobacco Smoke Pollution; D016753:Interleukin-10; D012710:Serum Albumin, Bovine; D007371:Interferon-gamma; D006433:Hemocyanins; C032808:keyhole-limpet hemocyanin; D001507:Beclomethasone