Protection against platelet-activating factor-induced injury by interferon inducer in perfused rabbit lung.
Platelet-activating factor (PAF) and the interferons (IFN) are released during sepsis and the adult respiratory distress syndrome. The proinflammatory nature of PAF and anti-inflammatory property of IFN led us to investigate interactions between these two mediators in an isolated perfused lung (IPL) preparation. In the IPL, mean pulmonary arterial pressure (Ppa), lung weight gain, and peak airway pressure (Paw) were monitored continuously for 1 h in six groups of rabbits: 1) control, 2) the IFN-alpha/beta inducer polyinosinic:cytidylic acid (polyI:C) alone, 3) PAF alone, 4) polyI:C + PAF, 5) indomethacin + PAF, and 6) AA861 (a 5-lipoxygenase inhibitor) + PAF. At the end of 1 h, microvascular pressure was determined by double-occlusion technique and partition of total pulmonary vascular resistance (RT) was calculated. Serial eicosanoid concentrations in the perfusate also were measured. PAF increased Ppa, Paw, lung weight gain, and RT. These changes were associated with increased thromboxane B2 and decreased leukotriene production. PolyI:C, which induced high levels of serum IFN in rabbits, blocked the PAF-induced increase in Ppa, Paw, lung weight gain, and RT, similar to indomethacin and AA861. PolyI:C suppressed PAF-stimulated release of thromboxane B2 and increased leukotriene levels in the perfusate. The PAF-induced lung responses also were attenuated by pretreatment with human recombinant IFN. These data indicate that polyI:C protects against PAF-induced responses in the rabbit IPL, most likely via its induction of IFN. This effect is related in part to inhibition of thromboxane A2 production stimulated by PAF and leukotrienes.
Huang
Y C
YC
Department of Medicine, Duke University Medical Center, Durham, North Carolina 27710.
Kennedy
T P
TP
Su
Y F
YF
Watkins
W D
WD
Whorton
A R
AR
Piantadosi
C A
CA
D000818:Animals; D001095:Arachidonic Acids / Q000378:metabolism / Q000494:pharmacology; D016227:Benzoquinones / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D016084:Bronchoconstriction / Q000187:drug effects; D006801:Humans; D006976:Hypertension, Pulmonary / Q000503:physiopathology / Q000517:prevention & control; D066298:In Vitro Techniques; D007202:Indicators and Reagents; D007213:Indomethacin / Q000494:pharmacology; D007369:Interferon Inducers / Q000494:pharmacology*; D007370:Interferon Type I / Q000494:pharmacology; D016859:Lipoxygenase Inhibitors / Q000494:pharmacology; D008171:Lung Diseases / Q000139:chemically induced / Q000503:physiopathology / Q000517:prevention & control*; D008297:Male; D008833:Microcirculation / Q000187:drug effects; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors* / Q000633:toxicity; D011070:Poly I-C / Q000494:pharmacology; D011654:Pulmonary Edema / Q000503:physiopathology / Q000517:prevention & control; D011817:Rabbits; D011994:Recombinant Proteins; D014655:Vascular Resistance / Q000187:drug effects
D001095:Arachidonic Acids; D016227:Benzoquinones; D007202:Indicators and Reagents; D007369:Interferon Inducers; D007370:Interferon Type I; D016859:Lipoxygenase Inhibitors; D010972:Platelet Activating Factor; D011994:Recombinant Proteins; C036837:2,3,5-trimethyl-6-(12-hydroxy-5,10-dodecadiynyl)-1,4-benzoquinone; D011070:Poly I-C; D007213:Indomethacin