Ocular inflammation stimulated by the immunomodulator AS101 [ammonium trichloro(dioxyethelene-O-O') tellurate].
The purpose of this study was to investigate the effect of a novel immunomodulator, AS101 [ammonium trichloro(dioxyethelene-O-O') tellurate], in the eye. Lewis rats were injected intravitreally with AS101 at a concentration of 13 micrograms/ml in one eye and BSS in the contralateral eye. Control animals were injected with BSS into the central vitreous of both eyes. Ocular inflammation was evaluated at 20 hours by histology, immunopathology, and by cell count, protein and cytokine measurement in the aqueous humor. At 20 hours, eyes injected with AS101 developed iridocyclitis and mild vitritis versus minimal inflammation and/or protein in contralateral eyes or eyes of control animals (p = 0.0121). The inflammatory infiltrate was mixed in character. Major Histocompatibility Complex (MHC) class II antigens and intercellular adhesion molecules (ICAM-1) were expressed in the anterior segment of eyes injected with AS101. In the aqueous humor of these eyes there were significant quantities of inflammatory cells, protein (mean +/- SEM = 11.2 +/- 2.3 mg/ml) and the cytokine interleukin 6 (IL-6) (450 units/ml) compared with contralateral eyes (p = 0.0005 for inflammatory cells; protein, mean +/- SEM = 1.6 +/- 0.17 mg/ml; IL-6 = 12 units/ml) and both eyes of control animals injected with BSS (p = 0.8955 for inflammatory cells; protein, OD = 1.5 mg/ml, OS = 0.7 mg/ml; IL-6, OD = 8 units/ml, OS = 13 units/ml). AS101 has a local inflammatory effect in the eye. This compound may activate ocular inflammation by releasing cytokines such as IL-6.
Laboratory of Immunology, National Eye Institute, National Institutes of Health, Bethesda, MD 20892.
K
K
Dastgheib
N
N
Hikita
B
B
Sredni
M
M
Albeck
D
D
Sredni
R B
RB
Nussenblatt
C C
CC
Chan
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D000869:Anterior Eye Segment / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D005030:Ethylenes / Q000494:pharmacology*; D005128:Eye Diseases / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology; D005260:Female; D000949:Histocompatibility Antigens Class II / Q000378:metabolism; D007249:Inflammation; D007267:Injections; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D015863:Iridocyclitis / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology; D051381:Rats; D011917:Rats, Inbred Lew; D014822:Vitreous Body / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology
D000276:Adjuvants, Immunologic; D005030:Ethylenes; D000949:Histocompatibility Antigens Class II; D015850:Interleukin-6; D018799:Intercellular Adhesion Molecule-1; C054105:ammonium trichloro(dioxoethylene-O,O'-)tellurate