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Interleukin‐2‐induced lung permeability is mediated by leukotriene B 4
Author(s) -
Klausner Joseph M.,
Goldman Gideon,
Skornick Yehuda,
Valeri Robert,
Inbar Moshe,
Shepro David,
Hechtman Herbert B.
Publication year - 1990
Publication title -
cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.052
H-Index - 304
eISSN - 1097-0142
pISSN - 0008-543X
DOI - 10.1002/1097-0142(19901201)66:11<2357::aid-cncr2820661118>3.0.co;2-j
Subject(s) - medicine , lymph , leukotriene b4 , vascular permeability , lung , leukotriene , endocrinology , pathology , inflammation , asthma
Interleukin (IL)‐2 therapy leads to respiratory dysfunction due to increased vascular permeability. This study examines the role of the chemoattractant, immunomodulator, and permeability‐promoting agent leukotriene (LT) B 4 in this setting. Sheep with chronic lung lymph fistulae were given IL‐2, 10 5 U/kg as an IV bolus (n = 6). Within 2 hours this led to a significant increase in LTB 4 levels in both plasma and lung lymph. the mean pulmonary artery pressure (MPAP) rose while the pulmonary artery wedge pressure was unchanged. Arterial oxygen tension (PaO 2 ) fell. Lung lymph flow (QL) was tripled ( P < 0.05) at 3 hours, coinciding with an increase in the lymph/plasma (L/P) protein ratio ( P < 0.05) resulting in an increase in the lymph protein clearance ( P < 0.05), data documenting increased microvascular permeability to protein. Mild leukopenia and thrombocytopenia ( P < 0.05) occurred. Body temperature rose and shaking chills were common. Pretreatment with the lipoxygenase inhibitor diethylcarbamazine (DEC; n = 6) reduced baseline plasma LTB 4 levels and prevented the IL‐2‐induced increases in LTB 4 in plasma and lung lymph ( P < 0.05). in contrast to IL‐2 treatment alone, DEC blunted the increase in MPAP and prevented the rises in QL ( P < 0.05), L/P protein ratio ( P < 0.05), and lymph protein clearance ( P < 0.05). DEC also prevented the IL‐2‐induced leukopenia, the fall in platelet count, and the rise in body temperature ( P < 0.05, respectively). Infusion of IL‐2 excipient control (n = 5) did not affect plasma or lymph LTB 4 levels but there were mild increases in MPAP ( P < 0.05). the QL also rose but this occurred while the L/P protein ratio fell ( P < 0.05). Body temperature rose moderately. the PaO 2 , leukocyte, and platelet counts were unaffected. These data indicate that IL‐2 administration leads to pulmonary dysfunction manifest by pulmonary hypertension and increased vascular permeability, events associated with LTB 4 synthesis and prevented by DEC. Leukotriene B 4 appears therefore to mediate the IL‐2‐induced lung injury.