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Departments of 1 Surgery and 2 Medicine, University of Colorado Health Sciences Center, Denver, Colorado 80262; and 3 Department of Surgery, Northwestern University, Chicago, Illinois 60611
Interleukin (IL)-11, like other members of the
gp130 receptor class, possesses anti-inflammatory properties. We
hypothesized that IL-11 pretreatment would attenuate endotoxin
[lipopolysaccharide (LPS)]-induced lung inflammation
and diminish injury to endothelium-dependent and -independent
mechanisms of pulmonary vasorelaxation that require cGMP in
Sprague-Dawley rats. LPS (20 mg/kg ip) increased lung tumor necrosis
factor (TNF)-
compared with the saline control (0.7 ± 0.15 ng/g lung wet wt for control vs. 3.5 ± 0.09 ng/g lung wet wt for LPS; P < 0.05). IL-11
(200 mg/kg ip) injected 10 min before LPS administration attenuated the
LPS-induced lung TNF- levels (1.6 ± 0.91 ng/g lung wet wt;
P < 0.05 vs. LPS). IL-11 also
diminished LPS-induced lung neutrophil sequestration as assessed by
myeloperoxidase units (2.1 ± 0.25 U/g lung wet wt for saline and
15.6 ± 2.02 U/g lung wet wt for LPS vs. 7.07 ± 1.65 U/g lung wet wt for LPS plus IL-11; P < 0.05). Similarly, TNF- binding protein (175 mg/kg) attenuated
LPS-induced myeloperoxidase activity (6.04 ± 0.14 U/g lung wet wt;
P < 0.05). Both IL-11 and TNF- binding protein similarly attenuated LPS-induced endothelium-dependent vasomotor dysfunction with improved relaxation responses to
10
7 and
106 M acetylcholine and
A-23187 in phenylephrine-preconstricted isolated pulmonary artery rings
(P < 0.05 vs. LPS).
Endothelium-independent relaxation responses to sodium nitroprusside
were also improved after LPS at 106 M
(P < 0.05 vs. LPS). Moreover, IL-11
decreased endotoxin-induced mortality in CF1 mice from 90 to 50%
(P 
0.05 vs. LPS). Therefore, IL-11
prevents LPS-induced lung TNF- production, neutrophil sequestration, and pulmonary vasomotor dysfunction. We conclude that IL-11 possesses anti-inflammatory activity that protects against LPS-induced lung injury and lethality.
tumor necrosis factor-; neutrophil; lung myeloperoxidase; guanosine 3',5'-cyclic monophosphate; gp130
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