Inhalative vs. systemic IL-10 administration: differences in the systemic inflammatory response and end-organ inflammation following hemorrhagic shock.
Interleukin-10 is known to modulate the systemic inflammatory response after trauma. This study investigates differences in the systemic and end-organ inflammation in animals treated with either inhalative or systemic IL-10 after experimental hemorrhagic shock (HS). Pressure controlled HS was performed in C57/BL6 mice for 1.5h (6 animals per group). Inhalative or systemic recombinant mouse IL-10 (50 μg/kg dissolved in 50 μl PBS) was administered after resuscitation. Animals were sacrificed after 4.5 or 22.5h of recovery. Serum levels of IL-6, IL-10, KC, MCP-1, and LBP were determined by ELISA. Pulmonary and liver inflammation was analyzed by standardized Myeloperoxidase (MPO) kits. Systemic and inhalative IL-10 administration affected the systemic inflammatory response as well as end-organ inflammation differently. Differences were obvious in the early (6h) but not later (24h) inflammatory phase. Systemic IL-10 application was associated with a decreased systemic inflammatory response as well as hepatic inflammation, whereas nebulized IL-10 solely reduced the pulmonary inflammation. Our study demonstrates that systemic and nebulized IL-10 administration differentially influenced the systemic cytokine response and end-organ inflammation. Early pulmonary but not hepatic protection appears to be possible by inhalative IL-10 application. Further studies are necessary to assess exact pathways.
Department of Orthopaedic and Trauma Surgery, University Hospital RWTH Aachen, Germany. rpfeifer@ukaachen.de
Roman
R
Pfeifer
Philipp
P
Lichte
Helen
H
Schreiber
Richard M
RM
Sellei
Joachim
J
Schmidt
Derek
D
Dombroski
Hans-Christoph
HC
Pape
Philipp
P
Kobbe
D000209:Acute-Phase Proteins; D000280:Administration, Inhalation; D000818:Animals; D002352:Carrier Proteins / Q000097:blood; D018932:Chemokine CCL2 / Q000097:blood; D004797:Enzyme-Linked Immunosorbent Assay; D006505:Hepatitis / Q000097:blood / Q000150:complications / Q000517:prevention & control*; D007249:Inflammation / Q000097:blood / Q000150:complications / Q000517:prevention & control*; D007269:Injections, Intra-Arterial; D016753:Interleukin-10 / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*; D015850:Interleukin-6 / Q000097:blood; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008168:Lung / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D008562:Membrane Glycoproteins / Q000097:blood; D051379:Mice; D008810:Mice, Inbred C57BL; D009195:Peroxidase / Q000378:metabolism; D011014:Pneumonia / Q000097:blood / Q000150:complications / Q000517:prevention & control*; D012771:Shock, Hemorrhagic / Q000150:complications*; D013997:Time Factors; D000099231:Lipopolysaccharide-Binding Protein
D000209:Acute-Phase Proteins; D002352:Carrier Proteins; D018932:Chemokine CCL2; D016753:Interleukin-10; D015850:Interleukin-6; D008562:Membrane Glycoproteins; D009195:Peroxidase; D000099231:Lipopolysaccharide-Binding Protein; C491768:Ccl2 protein, mouse