The effects of injury magnitude on the kinetics of the acute phase response.
BACKGROUND
The acute-phase response (APR) is critical to the body's ability to successfully respond to injury. A murine model of closed unilateral femur fractures and bilateral femur fracture were used to study the effect of injury magnitude on this response.


METHODS
Standardized unilateral femur fracture and bilateral femur fracture in mice were performed. The femur fracture sites, livers, and serum were harvested over time after injury. Changes in mRNA expression of cytokines, hepatic acute-phase proteins, and serum cytokines overtime were measured.


RESULTS
There was a rapid and short-lived hepatic APR to fracture injuries. The overall pattern in both models was similar. Both acute-phase proteins' mRNA (fibrinogen-γ and serum amyloid A-3) showed increased mRNA expression over baseline within the first 48 hours and their levels positively correlated with the extent of injury. However, increased severity of injury resulted in a delayed induction of the APR. A similar effect on the gene expression of cytokines (interleukin [IL]-1β, IL-6, and tumor necrosis factor-α) at the fracture site was seen. Serum IL-6 levels increased with increased injury and showed no delay between injury models.


CONCLUSIONS
Greater severity of injury resulted in a delayed induction of the liver's APR and a diminished expression of cytokines at the fracture site. Serum IL-6 levels were calibrated to the extent of the injury, and changes may represent mechanisms by which the local organ responses to injury are regulated by the injury magnitude.
Bauzá
Graciela
G
Department of Surgery, Boston University School of Medicine, Boston, Massachusetts, USA.
Miller
Glenn
G
Kaseje
Neema
N
Wigner
Nathan A
NA
Wang
Zhongyan
Z
Gerstenfeld
Louis C
LC
Burke
Peter A
PA
D000209:Acute-Phase Proteins / Q000096:biosynthesis / Q000235:genetics*; D000210:Acute-Phase Reaction / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005264:Femoral Fractures / Q000235:genetics* / Q000378:metabolism; D015870:Gene Expression; D015850:Interleukin-6 / Q000096:biosynthesis / Q000235:genetics; D008099:Liver / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000235:genetics*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000235:genetics
D000209:Acute-Phase Proteins; D015850:Interleukin-6; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha