Regulatory effects of interleukin-11 during acute lung inflammatory injury.
The role of interleukin-11 (IL-11) was evaluated in the IgG immune complex model of acute lung injury in rats. IL-11 mRNA and protein were both up-regulated during the course of this inflammatory response. Exogenously administered IL-11 substantially reduced, in a dose-dependent manner, the intrapulmonary accumulation of neutrophils and the lung vascular leak of albumin. These in vivo anti-inflammatory effects of IL-11 were associated with reduced NF-kappaB activation in lung, reduced levels of tumor necrosis factor alpha (TNF-alpha) in bronchoalveolar lavage (BAL) fluids, and diminished up-regulation of lung vascular ICAM-1. It is interesting that IL-11 did not affect BAL fluid content of the CXC chemokines, macrophage inflammatory protein-2 (MIP-2) and cytokine-inducible neutrophil chemoattractant (CINC); the presence of IL-11 did not affect these chemokines. However, BAL content of C5a was reduced by IL-11. These data indicate that IL-11 is a regulatory cytokine in the lung and that, like other members of this family, its anti-inflammatory properties appear to be linked to its suppression of NF-kappaB activation, diminished production of TNF-alpha, and reduced up-regulation of lung vascular ICAM-1.
Department of Surgery, University of Louisville School of Medicine, Kentucky 40202, USA. ablent01@ulkyvm.louisville.edu
A B
AB
Lentsch
L D
LD
Crouch
J A
JA
Jordan
B J
BJ
Czermak
E C
EC
Yun
R
R
Guo
V
V
Sarma
K M
KM
Diehl
P A
PA
Ward
D000818:Animals; D000936:Antigen-Antibody Complex / Q000276:immunology; D018893:Bronchoalveolar Lavage; D002630:Chemotactic Factors / Q000378:metabolism; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D017370:Interleukin-11 / Q000235:genetics / Q000276:immunology* / Q000494:pharmacology; D008297:Male; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism; D009504:Neutrophils / Q000276:immunology / Q000378:metabolism; D011014:Pneumonia / Q000276:immunology* / Q000473:pathology; D011650:Pulmonary Alveoli / Q000276:immunology; D051381:Rats; D020332:Rats, Inbred LEC; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D000936:Antigen-Antibody Complex; D002630:Chemotactic Factors; D007074:Immunoglobulin G; D017370:Interleukin-11; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1