Monoclonal antibody against CD11b/CD18 inhibits endotoxin-induced uveitis.
OBJECTIVE
To examine the serial expression of cell adhesion molecules in C3H/HeN mice with endotoxin-induced uveitis, and to study the effect of treatment with a monoclonal antibody against Mac-1 on the development of endotoxin-induced uveitis.


METHODS
Immunohistochemical staining was used to document the serial expression of Mac-1, intercellular adhesion molecule-1 (ICAM-1), and lymphocyte function-associated antigen-1 (LFA-1) in eyes of C3H/HeN mice with endotoxin-induced uveitis. Then, in two separate experiments, endotoxin-induced uveitis was produced in a total of 48 mice by injecting Salmonella typhimurium endotoxin into one hind footpad. At the time of endotoxin injection, 24 mice received an intraperitoneal injection of anti-Mac-1 antibody and 24 control mice received an intraperitoneal injection of rat IgG. Histopathologic sections of eyes taken 24 hours after endotoxin injection were graded by two masked observers on a scale of 0 to 4.


RESULTS
Intercellular adhesion molecule-1 was first expressed on the ciliary body epithelium 6 hr after endotoxin injection and Mac-1 and LFA-1 were expressed on infiltrating inflammatory cells 12 hr after endotoxin injection. Treatment with anti-MAC-1 antibody significantly inhibited the development of ocular inflammation when compared with treatment with control IgG (P < 0.001).


CONCLUSIONS
Intercellular adhesion molecule-1 is expressed in the eye before clinical or histologic signs of inflammation. Furthermore, treatment with antibody against Mac-1 significantly inhibits the development of endotoxin-induced uveitis in mice and suggests that anti-Mac-1 antibody may be useful for treating acute ocular inflammation.
Whitcup
S M
SM
Laboratory of Immunology, National Eye Institute, National Institutes of Health, Bethesda, Maryland 20892.
DeBarge
L R
LR
Rosen
H
H
Nussenblatt
R B
RB
Chan
C C
CC
D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D015703:Antigens, CD / Q000276:immunology*; D001427:Bacterial Toxins; D018821:CD18 Antigens; D015815:Cell Adhesion Molecules / Q000276:immunology; D002924:Ciliary Body / Q000276:immunology; D004731:Endotoxins; D005260:Female; D007124:Immunoenzyme Techniques; D007167:Immunotherapy; D016177:Macrophage-1 Antigen / Q000276:immunology*; D051379:Mice; D008809:Mice, Inbred C3H; D010857:Pigment Epithelium of Eye / Q000276:immunology; D014606:Uveitis, Anterior / Q000473:pathology / Q000517:prevention & control*
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D001427:Bacterial Toxins; D018821:CD18 Antigens; D015815:Cell Adhesion Molecules; D004731:Endotoxins; D016177:Macrophage-1 Antigen; C027952:salmonella toxin