Anti-tumor necrosis factor alpha therapy suppresses the induction of experimental autoimmune uveoretinitis in mice by inhibiting antigen priming.
OBJECTIVE
Experimental autoimmune uveoretinitis (EAU) serves as a model for several immune-mediated diseases that affect the eye in humans. Previous studies indicated that tumor necrosis factor alpha (TNF-alpha) has an important proinflammatory role in EAU and possibly in human uveitis. In this study, the authors investigated the effect of anti-TNF-alpha therapy on EAU in mice.


METHODS
Experimental autoimmune uveoretinitis was induced in B10.A mice by immunization with interphotoreceptor retinoid-binding protein (IRBP). The mice were treated with 100 or 300 microliters rabbit antiserum or polyclonal antibodies to human TNF-alpha. The treatment spanned either the afferent or the efferent stage of EAU (days -1, 1, 3, 5, 7, or days 8, 10, 12, 14, 16, respectively). Control animals were injected with preimmune rabbit serum at the corresponding times or were not treated. Three weeks after immunization, EAU was assessed by clinical evaluation and by histopathology. Immunologic responses were assessed by delayed-type hypersensitivity (DTH), lymphocyte proliferation to IRBP, and relative abundance of IRBP-primed splenocytes.


RESULTS
The treatment with rabbit anti-TNF-alpha serum significantly ameliorated disease when given during the afferent stage but had no effect when given during the efferent stage of EAU. The effect on DTH, lymphocyte proliferation, and abundance of antigen-reactive cells roughly paralleled the effect on disease.


CONCLUSIONS
Neutralization of systemic TNF ameliorates EAU. The effectiveness of afferent treatment in comparison to the treatment during the efferent stage, together with the reduced proliferation and the reduced abundance of IRBP-responsive cells, suggest that interference with afferent-acting processes such as antigen priming is important to achieve protection from EAU by anti-TNF treatment.
Sartani
G
G
Laboratory of Immunology, National Eye Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Silver
P B
PB
Rizzo
L V
LV
Chan
C C
CC
Wiggert
B
B
Mastorakos
G
G
Caspi
R R
RR
D000818:Animals; D000906:Antibodies / Q000627:therapeutic use*; D001324:Autoantigens / Q000276:immunology*; D001327:Autoimmune Diseases / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D004195:Disease Models, Animal; D005136:Eye Proteins / Q000276:immunology; D005260:Female; D006968:Hypersensitivity, Delayed / Q000276:immunology; D007114:Immunization; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D011817:Rabbits; D011994:Recombinant Proteins / Q000276:immunology; D012173:Retinitis / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D012177:Retinol-Binding Proteins / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology*; D015866:Uveitis, Posterior / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D000099214:Retinol-Binding Proteins, Interstitial
D000906:Antibodies; D001324:Autoantigens; D005136:Eye Proteins; D011994:Recombinant Proteins; D012177:Retinol-Binding Proteins; D014409:Tumor Necrosis Factor-alpha; D000099214:Retinol-Binding Proteins, Interstitial