The role of IL-5 in bleomycin-induced pulmonary fibrosis.
Eosinophils are known to express cytokines capable of promoting fibrosis. Interleukin-5 (IL-5) is important in regulating eosinophilopoiesis, eosinophil recruitment and activation. Lung IL-5 expression is elevated in pulmonary fibrosis, wherein the eosinophil is a primary source of fibrogenic cytokines. To determine the role of IL-5 in pulmonary fibrosis, the effects of anti-IL-5 antibody were investigated in a model of bleomycin-induced pulmonary fibrosis. Fibrosis was induced in mice by endotracheal bleomycin treatment. Animals were also treated with either anti-IL-5 antibody or control IgG. Lungs were then analyzed for fibrosis, eosinophil influx, chemotactic activity, and cytokine expression. The results show that a primary chemotactic activity at the height of eosinophil recruitment is IL-5. Furthermore, anti-IL-5 antibody caused significant reduction in lung eosinophilia, cytokine expression, and fibrosis. These findings taken together suggest an important role for IL-5 in pulmonary fibrosis via its ability to regulate eosinophilic inflammation, and thus eosinophil-dependent fibrogenic cytokine production.
Gharaee-Kermani
M
M
Department of Pathology, University of Michigan Medical School, Ann Arbor 48109-0602, USA.
McGarry
B
B
Lukacs
N
N
Huffnagle
G
G
Egan
R W
RW
Phan
S H
SH
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology / Q000627:therapeutic use; D001761:Bleomycin / Q000009:adverse effects*; D004804:Eosinophils / Q000378:metabolism / Q000502:physiology*; D005260:Female; D015848:Interleukin-5 / Q000037:antagonists & inhibitors / Q000276:immunology / Q000502:physiology*; D008168:Lung / Q000473:pathology; D051379:Mice; D008808:Mice, Inbred CBA; D011658:Pulmonary Fibrosis / Q000139:chemically induced* / Q000503:physiopathology / Q000517:prevention & control; D013047:Specific Pathogen-Free Organisms
D000911:Antibodies, Monoclonal; D015848:Interleukin-5; D001761:Bleomycin