Mice deficient in tumor necrosis factor receptors p55 and p75, interleukin-4, or inducible nitric oxide synthase are susceptible to endotoxin-induced uveitis.
OBJECTIVE
To investigate the roles of tumor necrosis factor-alpha (TNF-alpha), interleukin-4 (IL-4), and inducible nitric oxide synthase (iNOS) in endotoxin-induced uveitis (EIU) using gene knock-out mice.


METHODS
Mice (C57BL/6 x 129) either of normal phenotype or deficient in the genes encoding one or both tumor necrosis factor receptors (TNFR p55 and TNFR p75), IL-4, or iNOS were given footpad injections of 400 micrograms Escherichia coli lipopolysaccharide. Animals were killed 24 hours later, and infiltrating cells were counted on 5-micron ocular cross-sections through the optic nerve.


RESULTS
All abnormal mouse phenotypes were susceptible to EIU. Yet, TNFR p55 and IL-4 gene knock-out mice experienced less ocular inflammation than control animals (P = 0.021 and 0.007, respectively), whereas disease was not reduced for iNOS-deficient mice. Mice deficient in TNFR p55 and TNFR p75 experienced milder EIU than mice lacking TNFR p75 alone (P = 0.046).


CONCLUSIONS
Mice deficient in TNFR p55 and TNFR p75, IL-4, or iNOS retain the susceptibility to EIU, but TNF-alpha and IL-4 influence the influx of inflammatory cells to the eye during this disease.
Smith
J R
JR
Department of Ophthalmology, Flinders University of South Australia, Bedford Park, Australia.
Hart
P H
PH
Coster
D J
DJ
Williams
K A
KA
D000208:Acute Disease; D000818:Animals; D000869:Anterior Eye Segment / Q000473:pathology; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D002452:Cell Count; D004198:Disease Susceptibility; D004926:Escherichia coli; D005260:Female; D015847:Interleukin-4 / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D008070:Lipopolysaccharides / Q000633:toxicity*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout / Q000235:genetics; D019001:Nitric Oxide Synthase / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D052247:Nitric Oxide Synthase Type II; D018124:Receptors, Tumor Necrosis Factor / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D047888:Receptors, Tumor Necrosis Factor, Type I; D047889:Receptors, Tumor Necrosis Factor, Type II; D014606:Uveitis, Anterior / Q000139:chemically induced / Q000209:etiology* / Q000473:pathology / Q000503:physiopathology
D015703:Antigens, CD; D008070:Lipopolysaccharides; D018124:Receptors, Tumor Necrosis Factor; D047888:Receptors, Tumor Necrosis Factor, Type I; D047889:Receptors, Tumor Necrosis Factor, Type II; D015847:Interleukin-4; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse