Inhibition of experimental autoimmune uveoretinitis with anti-macrophage migration inhibitory factor antibodies.
OBJECTIVE
The role of macrophage migration inhibitory factor (MIF) in the regulation of ocular autoimmune disease was studied in experimental autoimmune uveoretinitis (EAU) in rats following immunization with a retinal antigen (Ag), interphotoreceptor retinoid-binding protein (IRBP).


METHODS
LEW rats were immunized with a single injection of IRBP derived peptide, R16(ADGSSWEGVGVVPDV). A neutralizing monoclonal antibody (mAb, IgM) to MIF was injected intraperitoneally every second day from day 0 to day 6 (group A), or from day 8 to day 14 (group B). Control rats were treated with unrelated mouse IgM or PBS. T cell proliferative responses were measured 12 days after immunization. The occurrence and severity of EAU were observed and compared among experimental and control groups.


RESULTS
T cell proliferative responses against R16 were inhibited in rats treated with anti-MIF mAb compared with the control rats. The development of EAU was delayed in the rats of group A in comparison with those of group B and the control group. The mean histological EAU score on day 18 in group A was 1.11 +/- 0. 11 and significantly lower than those of the group B (1.29 +/- 0.19) and the control (1.67 +/- 0.19).


CONCLUSIONS
The present result suggests that MIF plays an important role in induction of EAU.
Kitaichi
N
N
Department of Ophthalmology, School of Medicine, Institute of Immunological Science, Sapporo, Japan.
Matsuda
A
A
Kotake
S
S
Namba
K
K
Tagawa
Y
Y
Sasamoto
Y
Y
Ogasawara
K
K
Iwabuchi
K
K
Onoé
K
K
Matsuda
H
H
Nishihira
J
J
D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000627:therapeutic use*; D001327:Autoimmune Diseases / Q000139:chemically induced / Q000517:prevention & control*; D005123:Eye / Q000187:drug effects / Q000473:pathology; D005136:Eye Proteins; D007274:Injections, Intraperitoneal; D008263:Macrophage Migration-Inhibitory Factors / Q000276:immunology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000008:administration & dosage / Q000737:chemistry; D051381:Rats; D011917:Rats, Inbred Lew; D012173:Retinitis / Q000139:chemically induced / Q000517:prevention & control*; D012177:Retinol-Binding Proteins / Q000737:chemistry; D012720:Severity of Illness Index; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D014605:Uveitis / Q000139:chemically induced / Q000517:prevention & control*; D000099214:Retinol-Binding Proteins, Interstitial
D000911:Antibodies, Monoclonal; D005136:Eye Proteins; D008263:Macrophage Migration-Inhibitory Factors; D010446:Peptide Fragments; D012177:Retinol-Binding Proteins; D000099214:Retinol-Binding Proteins, Interstitial