OBJECTIVE: To determine the influence of the dose of collagen given nasally on the induction of specific mucosal tolerance in collagen-induced @entity625 . METHODS: The severity of clinical @entity625 induced in DBA/1 @entity19 was studied after the nasal administration (before disease induction) of 1 of 4 doses (across a 2-log range) of @entity291 type II collagen (CII). Parameters of immunity included lymphocyte proliferation and cytokine production in vitro in response to antigen stimulation, and the production of anticollagen IgG antibody subclasses. RESULTS: The 3 highest doses (20, 80, and 320 microg) ameliorated disease severity, whereas the lowest dose (5 microg) aggravated disease. These findings correlated well with antigen-specific T cell proliferation and cytokine and antibody production. T cell proliferation was suppressed by the higher doses of CII, whereas the low dose enhanced T cell proliferation, indicating it primed the T cells. Suppression of T cell proliferation could be overcome by the addition of exogenous @entity2047 ( @entity2047 ) to these cultures. Decreased T cell proliferation was associated with suppression of both @entity630 ( @entity60 [ @entity60 ]) and @entity61 ( @entity58 ) cytokines and all the subclasses of anticollagen IgG in @entity19 receiving 20, 80, or 320 microg of collagen. Overall, the highest dose of collagen (320 microg) was less effective at suppressing the immune response and disease than the 20-microg or 80-microg doses. There was an increased production of antibodies of all IgG isotypes, and of the @entity630 -associated cytokines @entity60 and @entity2047 , in animals that had received the lowest dose of 5 microg collagen nasally. CONCLUSION: Nasal administration of antigens is effective in inducing tolerance and reducing disease severity, but the effects are dose dependent. Low doses can prime the immune system and aggravate disease; high doses may not suppress disease. Suppression of the immune response, which correlates with @entity66 , is not obviously associated with a type I to type II T cell switch, but rather with an overall suppression of both forms of T cell response, with a potential role for anergy of T cells in this process.

Importance of dose of type II collagen in suppression of collagen-induced XXXX by nasal tolerance.

@entity291 :: ('9913', 'Species') :: ['bovine'] @entity625 :: ('MESH:D001168', 'Disease') :: ['arthritis'] @entity66 :: ('MESH:D004194', 'Disease') :: ['suppression of disease'] @entity2047 :: ('16183(Tax:10090)', 'Gene') :: ['IL-2', 'interleukin-2'] @entity19 :: ('10090', 'Species') :: ['mice'] @entity60 :: ('15978(Tax:10090)', 'Gene') :: ['interferon-gamma', 'IFNgamma'] @entity61 :: ('15111(Tax:10090)', 'Gene') :: ['Th2'] @entity58 :: ('16189(Tax:10090)', 'Gene') :: ['IL-4'] @entity630 :: ('57314(Tax:10090)', 'Gene') :: ['Th1']
@entity625 :: (MESH:D001168,Disease) :: ['arthritis']
