PMID- 1649146
OWN - NLM
STAT- MEDLINE
DCOM- 19910821
LR  - 20131121
IS  - 0146-0404 (Print)
IS  - 0146-0404 (Linking)
VI  - 32
IP  - 8
DP  - 1991 Jul
TI  - Lipid mediators of tumor necrosis factor-alpha-induced uveitis.
PG  - 2393-9
AB  - The authors tested the hypothesis that platelet-activating factor (PAF) and 
      cyclooxygenase metabolites of arachidonic acid mediate the ocular inflammatory 
      response to intravitreally injected tumor necrosis factor-alpha (TNF alpha). 
      Rabbits were treated with the PAF receptor antagonist SRI 63-441, the 
      cyclooxygenase inhibitors indomethacin and naproxen, or SRI 63-441 and 
      indomethacin. At 24 hr after intravitreal injection of TNF (20,000 U), the 
      severity of inflammation was assessed based on iridal hypermia, aqueous humor 
      leukocyte number and aqueous humor protein, immunoreactive-prostaglandin E 
      (I-PGE), and leukotriene B4 (LTB4) concentrations. Although all of the treatments 
      significantly reduced the severity of anterior uveitis, SRI 63-441 plus 
      indomethacin was the most effective, indomethacin and naproxen were 
      intermediately effective, and SRI 63-441 was the least effective. The results of 
      this study are consistent with an important role for cyclooxygenase metabolites 
      of arachidonic acid in the inflammatory response to TNF alpha, particularly with 
      respect to dilation of iridal blood vessels. Although naproxen was nearly as 
      effective as indomethacin in reducing aqueous humor I-PGE levels, indomethacin 
      conferred significantly more protection to the blood-aqueous barrier as shown by 
      lower protein levels in the aqueous humor. Thus, although cyclooxygenase 
      inhibition may partially explain the protection afforded the blood-aqueous 
      barrier by these nonsteroidal anti-inflammatory agents, the data suggest that 
      indomethacin may also exert anti-inflammatory effects that are independent of 
      cyclooxygenase inhibition. Furthermore, the data are consistent with TNF alpha 
      releasing PAF in the eye and PAF acting both directly, by increasing vascular 
      permeability, and indirectly, by promoting release of cyclooxygenase and 
      lipoxygenase metabolites of arachidonic acid.
FAU - Fleisher, L N
AU  - Fleisher LN
AD  - Department of Anatomy, North Carolina State University, College of Veterinary 
      Medicine, Raleigh, North Carolina 27606.
FAU - Ferrell, J B
AU  - Ferrell JB
FAU - Smith, M G
AU  - Smith MG
FAU - McGahan, M C
AU  - McGahan MC
LA  - eng
GR  - EY-08688/EY/NEI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Invest Ophthalmol Vis Sci
JT  - Investigative ophthalmology & visual science
JID - 7703701
RN  - 0 (Anti-Inflammatory Agents, Non-Steroidal)
RN  - 0 (Eicosanoids)
RN  - 0 (Eye Proteins)
RN  - 0 (Platelet Activating Factor)
RN  - 0 (Prostaglandins E)
RN  - 0 (Quinolinium Compounds)
RN  - 0 (Recombinant Proteins)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 104786-62-1 (SRI 63-441)
RN  - 1HGW4DR56D (Leukotriene B4)
RN  - 57Y76R9ATQ (Naproxen)
RN  - XXE1CET956 (Indomethacin)
SB  - IM
MH  - Animals
MH  - Anti-Inflammatory Agents, Non-Steroidal/pharmacology
MH  - Aqueous Humor/metabolism
MH  - Eicosanoids/*physiology
MH  - Eye Proteins/metabolism
MH  - Indomethacin/pharmacology/therapeutic use
MH  - Leukocyte Count
MH  - Leukotriene B4/metabolism
MH  - Male
MH  - Naproxen/pharmacology/therapeutic use
MH  - Platelet Activating Factor/antagonists & inhibitors
MH  - Prostaglandins E/metabolism
MH  - Quinolinium Compounds/pharmacology/therapeutic use
MH  - Rabbits
MH  - Recombinant Proteins/pharmacology
MH  - Tumor Necrosis Factor-alpha/*antagonists & inhibitors
MH  - Uveitis, Anterior/drug therapy/*etiology
MH  - Vitreous Body/drug effects
EDAT- 1991/07/01 00:00
MHDA- 1991/07/01 00:01
CRDT- 1991/07/01 00:00
PHST- 1991/07/01 00:00 [pubmed]
PHST- 1991/07/01 00:01 [medline]
PHST- 1991/07/01 00:00 [entrez]
PST - ppublish
SO  - Invest Ophthalmol Vis Sci. 1991 Jul;32(8):2393-9.