Prevention of interleukin 2-induced acute lung injury in guinea pigs by pentoxifylline.
We administered recombinant human interleukin 2 (IL-2) to guinea pigs to investigate whether IL-2 would cause acute lung injury. In addition, we examined the effects of pentoxifylline (PTXF) on IL-2-induced acute lung injury. Three groups of animals were studied over a period of 8 h. The saline control group was injected intravenously with 2 ml of pyrogen-free saline; the IL-2 group was injected intravenously with 4 X 10(6) U/kg recombinant IL-2; and the IL-2-PTXF group was injected with a 20-mg/kg bolus of PTXF followed by a continuous infusion (6 mg.kg-1.h-1) started 60 min before injection of 4 X 10(6) U/kg IL-2. Lung water (wet-to-dry lung weight ratio), the concentration ratios of 125I-albumin in bronchoalveolar lavage (BAL) fluid and lung tissue compared with plasma (125I-albumin BAL-to-plasma, 125I-albumin lung-to-plasma), and cell counts in BAL fluid were examined. An intravenous injection of IL-2 caused an increased lung water (P less than 0.01), an increased 125I-albumin lung-to-plasma ratio (P less than 0.05), and a significant increase in the absolute number of neutrophils, lymphocytes, and macrophages in BAL fluid compared with the saline control. In contrast, the PTXF-pretreated group did not demonstrate IL-2-induced acute lung injury (lung water, 125I-albumin lung-to-plasma) or increased accumulation of neutrophils, lymphocytes, and macrophages in the BAL. These data suggest a possible role for PTXF in attenuating the side effects of IL-2.
Ishizaka
A
A
Department of Medicine, Stanford University Medical Center, California 94035.
Hatherill
J R
JR
Harada
H
H
Yonemaru
M
M
Hoffmann
H
H
Zheng
H
H
O'Hanley
P T
PT
Raffin
T A
TA
D000208:Acute Disease; D000818:Animals; D006168:Guinea Pigs; D007376:Interleukin-2 / Q000009:adverse effects*; D008168:Lung / Q000187:drug effects; D055370:Lung Injury; D010431:Pentoxifylline / Q000494:pharmacology*; D013805:Theobromine / Q000031:analogs & derivatives*
D007376:Interleukin-2; D013805:Theobromine; D010431:Pentoxifylline