Suppression of S-antigen-induced experimental autoimmune uveoretinitis in Lewis rats by oral administration with CGS-13080, a thromboxane synthetase inhibitor.
Oral administration of CGS-13080 [imidazo (1, 5-alpha) pyridine-5-hexanoic acid], a thromboxane synthetase inhibitor, has been reported to cause a marked reduction in serum thromboxane B2 concentration in humans and animals. Since thromboxane metabolites play an important role in ocular inflammation, the effect of oral CGS-13080 in the development of experimental autoimmune uveoretinitis in Lewis rats has been investigated. Females were immunized with bovine S-antigen (S-Ag). Treatment was started on day 0 of immunization. Animals were divided into three groups. The control group was fed a standard pellet diet, while the treated groups were fed the standard diet supplemented with either a low dose (0.8 g per 10 kg pellet) or a high dose (1.6 g per 10 kg pellet) of CGS 13080. From day 10 after immunization, the eyes of these rats were examined daily for clinical evidence of experimental autoimmune uveoretinitis. On day 14, the eyes were collected for histologic study. The cellular immune responses were evaluated on the draining inguinal lymph nodes. Blood samples were also collected for the measurement of anti-S-Ag antibody production, thromboxane B2 and prostaglandin A2 levels. Clinical disease developed in 73.3% of the control rat group, 30.0% of the low-dose treated group and 17.6% of the high-dose group. The average histologic grade was 1.9 in the control group, 0.65 in low-dose group and 0.32 in high-dose group. Lymphocyte proliferation to S-Ag paralleled the clinical disease scores. Average stimulation indices were 10.9 in the controls, 7.5 in the low-dose group and 2.2 in the high-dose group.(ABSTRACT TRUNCATED AT 250 WORDS)
Li
Q
Q
Laboratory of Immunology, National Eye Institute, National Institutes of Health, Bethesda, MD 20892.
Lopez
J S
JS
Caspi
R R
RR
Roberge
F G
FG
Nussenblatt
R B
RB
Kador
P F
PF
Chan
C C
CC
D000818:Animals; D000941:Antigens / Q000276:immunology; D019393:Arrestin; D001324:Autoantigens / Q000276:immunology; D001327:Autoimmune Diseases / Q000517:prevention & control*; D002825:Chorioretinitis / Q000097:blood / Q000473:pathology / Q000517:prevention & control*; D002829:Choroid / Q000473:pathology; D015232:Dinoprostone / Q000097:blood; D005136:Eye Proteins / Q000276:immunology; D005260:Female; D007093:Imidazoles / Q000627:therapeutic use*; D007074:Immunoglobulin G / Q000096:biosynthesis; D008213:Lymphocyte Activation / Q000187:drug effects; D011725:Pyridines / Q000627:therapeutic use*; D051381:Rats; D011917:Rats, Inbred Lew; D012160:Retina / Q000473:pathology; D013929:Thromboxane B2 / Q000097:blood; D013930:Thromboxane-A Synthase / Q000037:antagonists & inhibitors*
D000941:Antigens; D019393:Arrestin; D001324:Autoantigens; D005136:Eye Proteins; D007093:Imidazoles; D007074:Immunoglobulin G; D011725:Pyridines; D013929:Thromboxane B2; C037787:pirmagrel; D013930:Thromboxane-A Synthase; D015232:Dinoprostone