Abstract
Abstract: :
Purpose: Many aspects of experimental autoimmune uveitis (EAU) resemble those of other autoimmune disease models such as experimental autoimmune encephalomyelitis (EAE). However, here we report on three systems in which EAU exhibited features different from those of other experimental diseases. Methods: Osteopontin –/– mice were created at Rutgers University, while CD1d –/– mice were generated at Vanderbilt University. Mice of these lines, their +/+ controls, and B10.A mice were immunized with IRBP by the conventional method for EAU induction, using 150 ug for the two KO mouse lines and 50 ug for the B10.A mice, along with 0.5 ug pertussis toxin. Disease severity was scored by histological examination. Treatment with atorvastatin was given daily by gavage, at 1 and 10 mg/Kg. Results: EAU induction was examined in three experimental systems in which development of other autoimmune diseases was shown to be modified: (i) Osteopontin –/– mice show reduced capacity to develop EAE (e.g., Chabas et al., Science, 294:1731). These mice, however, resembled their +/+ controls in developing EAU with similar levels of severity. (ii) CD1d –/– mice lack the immunomodulatory NKT cells and, consequently, exhibit enhanced susceptibility to autoimmune diseases such as diabetes (Godfrey et al., Imm. Today, 21:573). On the other hand, the CD1d –/– developed EAU similarly to their +/+ controls. (iii) Atorvastatin ("Lipitor") was reported to dramatically inhibit EAE in mice (Youssef et al., Nature, 420:78). Surprisingly, identical doses and treatment schedule with atorvastatin had minimal or no effect on development of EAU in B10.A mice. Conclusion: Unlike its close resemblance to other autoimmune diseases, EAU differed from these other experimental disease models in three systems, i.e., involvement of osteopontin in the pathogenesis of the disease, susceptibility to NKT cells and susceptibility to treatment with atorvastatin. Thus, information collected on other experimental autoimmune diseases cannot always be applied to EAU.
Keywords: immunomodulation/immunoregulation • cytokines/chemokines • drug toxicity/drug effects