title: Tumor necrosis factor-alpha is not essential in endotoxin induced eye inflammation: studies in cytokine receptor deficient mice.
abstract: OBJECTIVE
  Anterior uveitis frequently occurs in association with specific systemic inflammatory diseases. Interleukin 1 (IL-1) and tumor necrosis factor-alpha (TNF-alpha) have been implicated in the pathogenesis of these diseases. We evaluate the need for these cytokines in a model of anterior uveitis.
  
  
  METHODS
  Endotoxin was injected into the vitreous of mice deficient in IL-1 receptor type I, TNF receptors p55 and p75, both IL-1R1 and TNFR p55, or controls. Eyes were harvested after 24 h for histology and IL-6 bioassays or after 3 h for reverse transcriptase-polymerase chain reaction analysis of mRNA for specific cytokines or enzymes.
  
  
  RESULTS
  No significant difference in the number of infiltrating cells was found in TNFR p55/p75 deficient mice compared to controls in any of 4 separate experiments or in the combined data (p = 0.8). The number of infiltrating cells was significantly reduced in 2 of 4 experiments with IL-1R1 deficient mice (p < 0.001 based on combined data from 4 studies). IL-1R1/TNFR p55 deficient mice had a reduction in infiltrating cells in 2 of 3 experiments (p < 0.001 based on combined data from all studies). IL-6 levels were not significantly reduced in either of 2 experiments with TNFR p55/p75 deficient mice, but were reduced in one of 2 experiments with IL-1R1-/- mice (p = 0.02) and in one experiment with IL-1R1/TNFR p55 deficient mice (p = 0.01). In response to endotoxin, all 3 receptor deficient lines increased mRNA levels for IL-1-alpha, IL-10, TNF-alpha, IL-1 receptor antagonist, and inducible nitric oxide synthase.
  
  
  CONCLUSIONS
  IL-1 appears to have a more pivotal role in endotoxin induced uveitis than TNF-alpha, although neither cytokine is essential. Deletion of receptors for both cytokines has the most consistent effect, which is in accord with the hypothesis that these cytokines are, at least in part, functionally redundant.
authors.affiliation: Casey Eye Institute, Department of Cell and Developmental Biology, Oregon Health Sciences University, Portland 97201-4197, USA.
authors.forename: J T
authors.initials: JT
authors.lastname: Rosenbaum
authors.forename: Y B
authors.initials: YB
authors.lastname: Han
authors.forename: J M
authors.initials: JM
authors.lastname: Park
authors.forename: M
authors.initials: M
authors.lastname: Kennedy
authors.forename: S R
authors.initials: SR
authors.lastname: Planck
mesh_terms: D000818:Animals; D001082:Aqueous Humor / Q000187:drug effects / Q000378:metabolism; D004195:Disease Models, Animal; D004731:Endotoxins / Q000008:administration & dosage / Q000009:adverse effects*; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D007371:Interferon-gamma / Q000235:genetics; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1 / Q000235:genetics / Q000494:pharmacology; D016753:Interleukin-10 / Q000235:genetics; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism; D015603:Keratinocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D019001:Nitric Oxide Synthase / Q000235:genetics; D052247:Nitric Oxide Synthase Type II; D012333:RNA, Messenger / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D017472:Receptors, Interleukin-1 / Q000172:deficiency / Q000235:genetics; D018124:Receptors, Tumor Necrosis Factor / Q000172:deficiency / Q000235:genetics; D012795:Sialoglycoproteins / Q000235:genetics; D014409:Tumor Necrosis Factor-alpha / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D014606:Uveitis, Anterior / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism*; D014822:Vitreous Body / Q000187:drug effects / Q000378:metabolism / Q000473:pathology
chemical_list: D004731:Endotoxins; C507764:Il1rn protein, mouse; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1; D015850:Interleukin-6; D012333:RNA, Messenger; D017472:Receptors, Interleukin-1; D018124:Receptors, Tumor Necrosis Factor; D012795:Sialoglycoproteins; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D007371:Interferon-gamma; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse