Patterns of cytokine release and evolution of remote organ dysfunction after bilateral femur fracture.
The interaction between the complex pattern of cytokine release and remote organ dysfunction after trauma is incompletely understood. The aim of this study was to investigate the pattern of cytokine release and its association with the evolution of remote organ dysfunction after bilateral femur fracture. Male C57/BL6 mice were euthanized at six different time points (1-6 h) after bilateral femur fracture. Serum cytokine concentrations were measured with the Luminex multiplexing platform, and serum alanine aminotransferase levels were measured with the Vitros 950 Chemistry System. Hepatic and pulmonary myeloperoxidase activity was determined with an enzyme-linked immunosorbent assay kit. Permeability changes of the lung were assessed via bronchoalveolar lavage, and those of the liver via assessment of edema formation. Serum TNF-alpha was unchanged in the fracture group throughout the experiment. Serum IL-6 and keratinocyte levels peaked at 5 h postinjury, whereas IL-10 levels peaked at 2 and 6 h. A brief IL-1beta peak was observed at 3 h after fracture. Hepatic and pulmonary myeloperoxidase activity was significantly elevated within 1 h after trauma. Hepatic permeability was significantly increased within 2 h, and pulmonary permeability was significantly increased within 6 h after injury. Serum alanine aminotransferase levels peaked at 3 and 5 h postinjury. The pattern of serum IL-6, keratinocyte, IL-10, and IL-1beta release was dynamic, whereas no significant elevations in TNF-alpha were observed. The early hepatic and pulmonary infiltration of polymorphonuclear cells occurred in the absence of significantly elevated serum cytokine levels, suggesting that either early minor changes with an unbalance in inflammatory mediators or locally produced cytokines may initiate this process.
Department of Orthopedic Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania 15213, USA. kobbep@upmc.edu
Philipp
P
Kobbe
Yoram
Y
Vodovotz
David J
DJ
Kaczorowski
Kevin P
KP
Mollen
Timothy R
TR
Billiar
Hans-Christoph
HC
Pape
D000818:Animals; D016207:Cytokines / Q000378:metabolism*; D005264:Femoral Fractures / Q000150:complications* / Q000503:physiopathology*; D015850:Interleukin-6 / Q000097:blood; D015603:Keratinocytes / Q000166:cytology; D008099:Liver / Q000293:injuries; D055370:Lung Injury; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
D016207:Cytokines; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha