Tumor necrosis factor primes the effects of platelet-activating factor on rat vascular permeability.
The extravasation of Evans blue dye injected in the rat tail vein (EB, 20 mg/kg) was used as a measure of vascular permeability. When the animals were treated with tumor necrosis factor (TNF, 200 micrograms/kg), EB dye was recovered in much larger quantities than in controls in all organs, and especially in the trachea, lower bronchi, lung parenchyma, spleen, pancreas and duodenum (100% increases and over). The EB contents of higher bronchi, heart, liver and kidneys were less marked. The injection of TNF (200 micrograms/kg) 60 min before an injection of platelet-activating factor (PAF, 0.1 micrograms/kg) produced a synergism in many organs. The increases varied from 176 to 574% for the trachea, bronchi, lung parenchyma, pancreas, kidneys and duodenum. The increases in EB contents of the heart, spleen and liver were 86, 96 and 38% respectively. Human recombinant interleukin (IL-1 alpha, up to 400,000 U/kg) did not modify vascular permeability by itself nor primed the effect of PAF in our model. The combination of TNF and IL-1 alpha did not produce effects larger than those of TNF alone. These results further confirm the proinflammatory effects of PAF and its complex interactions with cytokines.
Sirois
M G
MG
Department of Pharmacology, Faculty of Medicine, University of Sherbrooke, Que., Canada.
Plante
G E
GE
Braquet
P
P
Sirois
P
P
D000818:Animals; D002199:Capillary Permeability / Q000187:drug effects*; D004357:Drug Synergism; D007249:Inflammation / Q000209:etiology; D007375:Interleukin-1 / Q000008:administration & dosage; D008297:Male; D009928:Organ Specificity; D010972:Platelet Activating Factor / Q000008:administration & dosage* / Q000502:physiology; D051381:Rats; D011919:Rats, Inbred Strains; D014409:Tumor Necrosis Factor-alpha / Q000008:administration & dosage*
D007375:Interleukin-1; D010972:Platelet Activating Factor; D014409:Tumor Necrosis Factor-alpha