Post-insult treatment with interleukin-1 receptor antagonist decreases oxidative lung injury in rats given intratracheal interleukin-1.
Systemic administration of recombinant human interleukin-1 receptor antagonist (IL-1Ra) caused a rapid and sustained elevation of plasma IL-1Ra levels and decreased the leak of intravascularly injected 125I-labeled albumin into lungs of rats given human recombinant interleukin-1 intratracheally. IL-1Ra treatment decreased leak when given 0.5 h before, 1.25 h after, or 2.5 h after IL-1 administration. Similarly, IL-1Ra treatment decreased lavage leukocytes and neutrophils when given 0.5 h before, 1.25 h after, or 2.5 h after IL-1 administration. Pretreatment with IL-1Ra also decreased lung myeloperoxidase activity and breath H2O2 concentration increases in rats given IL-1 intratracheally. Our results suggest that IL-1Ra treatment may decrease acute lung injury and neutrophil influx even when given after an IL-1 inciting insult.
Webb-Waring Institute for Biomedical Research, University of Colorado Health Sciences Center, Denver 80262.
J A
JA
Leff
M E
ME
Bodman
O J
OJ
Cho
S
S
Rohrbach
O K
OK
Reiss
J L
JL
Vannice
J E
JE
Repine
D000818:Animals; D001944:Breath Tests; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D006861:Hydrogen Peroxide / Q000032:analysis; D007375:Interleukin-1 / Q000502:physiology*; D008168:Lung / Q000201:enzymology / Q000473:pathology / Q000503:physiopathology; D008297:Male; D009504:Neutrophils / Q000473:pathology; D009195:Peroxidase / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017472:Receptors, Interleukin-1 / Q000037:antagonists & inhibitors*; D011994:Recombinant Proteins; D012128:Respiratory Distress Syndrome / Q000473:pathology / Q000503:physiopathology* / Q000628:therapy
D007375:Interleukin-1; D017472:Receptors, Interleukin-1; D011994:Recombinant Proteins; D006861:Hydrogen Peroxide; D009195:Peroxidase