Male gender is associated with excessive IL-6 expression following severe injury

Jason L. Sperry, Randall S. Friese, Heidi L. Frankel, Micheal A. West, Joseph Cuschieri, Ernest E. Moore, Brian G. Harbrecht, Andrew B. Peitzman, Timothy R. Billiar, Ronald V. Maier, Daniel G. Remick, Joseph P. Minei

Research output: Contribution to journalArticle

63 Citations (Scopus)

Abstract

OBJECTIVE: An important and persistent laboratory finding has been that males and females respond differently after traumatic injury and hemorrhagic shock. We have previously presented clinical data showing that male gender is independently associated with a 40% higher rate of multiple organ failure (MOF) and a 25% higher rate of nosocomial infection (NI) after injury; however, the mechanism responsible for this dimorphic response after injury has not been adequately characterized clinically. METHODS: Data were obtained from a multicenter prospective cohort study evaluating clinical outcomes in severely injured adults with blunt hemorrhagic shock. Proteomic analysis of serum inflammatory cytokines, on days 0, 1, and 4 postinjury, was performed on 46 males and 34 females. Repeated measures ANOVA were used to compare serial IL-1β, TNF-α, IL-6, IL-8, and IL-10 serum levels across gender, while controlling for important confounders. Logistic regression modeling was then used to analyze the independent risk of MOF and NI associated with gender. RESULTS: IL-6 serum levels were statistically higher in males relative to females (p = 0.008). This higher level of IL-6 expression in males remained statistically significant over time even after controlling for differences in age, initial base deficit, ISS, and 12-hour blood transfusion requirements (p = 0.025). No differences in IL-1β serum levels (p = 0.543), TNF-α, (p = 0.200) IL-8 (p = 0.107), and IL-10 (p = 0.157) were found. Males had a higher crude incidence of MOF and an 11-fold higher independent risk of MOF. CONCLUSIONS: Persistently elevated IL-6 levels in males are associated with a higher rate of MOF. It is not known if this excessive IL-6 expression in males is causal or only a marker for poor outcome. Further studies are required to elucidate if this early, persistent IL-6 expression is responsible for the gender-based differential outcomes after injury.

Original languageEnglish (US)
Pages (from-to)572-578
Number of pages7
JournalJournal of Trauma - Injury, Infection and Critical Care
Volume64
Issue number3
DOIs
StatePublished - Mar 2008

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Interleukin-6
Multiple Organ Failure
Wounds and Injuries
Hemorrhagic Shock
Cross Infection
Serum
Interleukin-8
Interleukin-1
Interleukin-10
Traumatic Shock
Blood Transfusion
Proteomics
Analysis of Variance
Cohort Studies
Logistic Models
Prospective Studies
Cytokines
Incidence

Keywords

  • Gender dimorphism
  • IL-6
  • Multiple system organ failure
  • Nosocomial infection

ASJC Scopus subject areas

  • Surgery

Cite this

Male gender is associated with excessive IL-6 expression following severe injury. / Sperry, Jason L.; Friese, Randall S.; Frankel, Heidi L.; West, Micheal A.; Cuschieri, Joseph; Moore, Ernest E.; Harbrecht, Brian G.; Peitzman, Andrew B.; Billiar, Timothy R.; Maier, Ronald V.; Remick, Daniel G.; Minei, Joseph P.

In: Journal of Trauma - Injury, Infection and Critical Care, Vol. 64, No. 3, 03.2008, p. 572-578.

Research output: Contribution to journalArticle

Sperry, JL, Friese, RS, Frankel, HL, West, MA, Cuschieri, J, Moore, EE, Harbrecht, BG, Peitzman, AB, Billiar, TR, Maier, RV, Remick, DG & Minei, JP 2008, 'Male gender is associated with excessive IL-6 expression following severe injury', Journal of Trauma - Injury, Infection and Critical Care, vol. 64, no. 3, pp. 572-578. https://doi.org/10.1097/TA.0b013e3181650fdf
Sperry, Jason L. ; Friese, Randall S. ; Frankel, Heidi L. ; West, Micheal A. ; Cuschieri, Joseph ; Moore, Ernest E. ; Harbrecht, Brian G. ; Peitzman, Andrew B. ; Billiar, Timothy R. ; Maier, Ronald V. ; Remick, Daniel G. ; Minei, Joseph P. / Male gender is associated with excessive IL-6 expression following severe injury. In: Journal of Trauma - Injury, Infection and Critical Care. 2008 ; Vol. 64, No. 3. pp. 572-578.
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abstract = "OBJECTIVE: An important and persistent laboratory finding has been that males and females respond differently after traumatic injury and hemorrhagic shock. We have previously presented clinical data showing that male gender is independently associated with a 40{\%} higher rate of multiple organ failure (MOF) and a 25{\%} higher rate of nosocomial infection (NI) after injury; however, the mechanism responsible for this dimorphic response after injury has not been adequately characterized clinically. METHODS: Data were obtained from a multicenter prospective cohort study evaluating clinical outcomes in severely injured adults with blunt hemorrhagic shock. Proteomic analysis of serum inflammatory cytokines, on days 0, 1, and 4 postinjury, was performed on 46 males and 34 females. Repeated measures ANOVA were used to compare serial IL-1β, TNF-α, IL-6, IL-8, and IL-10 serum levels across gender, while controlling for important confounders. Logistic regression modeling was then used to analyze the independent risk of MOF and NI associated with gender. RESULTS: IL-6 serum levels were statistically higher in males relative to females (p = 0.008). This higher level of IL-6 expression in males remained statistically significant over time even after controlling for differences in age, initial base deficit, ISS, and 12-hour blood transfusion requirements (p = 0.025). No differences in IL-1β serum levels (p = 0.543), TNF-α, (p = 0.200) IL-8 (p = 0.107), and IL-10 (p = 0.157) were found. Males had a higher crude incidence of MOF and an 11-fold higher independent risk of MOF. CONCLUSIONS: Persistently elevated IL-6 levels in males are associated with a higher rate of MOF. It is not known if this excessive IL-6 expression in males is causal or only a marker for poor outcome. Further studies are required to elucidate if this early, persistent IL-6 expression is responsible for the gender-based differential outcomes after injury.",
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T1 - Male gender is associated with excessive IL-6 expression following severe injury

AU - Sperry, Jason L.

AU - Friese, Randall S.

AU - Frankel, Heidi L.

AU - West, Micheal A.

AU - Cuschieri, Joseph

AU - Moore, Ernest E.

AU - Harbrecht, Brian G.

AU - Peitzman, Andrew B.

AU - Billiar, Timothy R.

AU - Maier, Ronald V.

AU - Remick, Daniel G.

AU - Minei, Joseph P.

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N2 - OBJECTIVE: An important and persistent laboratory finding has been that males and females respond differently after traumatic injury and hemorrhagic shock. We have previously presented clinical data showing that male gender is independently associated with a 40% higher rate of multiple organ failure (MOF) and a 25% higher rate of nosocomial infection (NI) after injury; however, the mechanism responsible for this dimorphic response after injury has not been adequately characterized clinically. METHODS: Data were obtained from a multicenter prospective cohort study evaluating clinical outcomes in severely injured adults with blunt hemorrhagic shock. Proteomic analysis of serum inflammatory cytokines, on days 0, 1, and 4 postinjury, was performed on 46 males and 34 females. Repeated measures ANOVA were used to compare serial IL-1β, TNF-α, IL-6, IL-8, and IL-10 serum levels across gender, while controlling for important confounders. Logistic regression modeling was then used to analyze the independent risk of MOF and NI associated with gender. RESULTS: IL-6 serum levels were statistically higher in males relative to females (p = 0.008). This higher level of IL-6 expression in males remained statistically significant over time even after controlling for differences in age, initial base deficit, ISS, and 12-hour blood transfusion requirements (p = 0.025). No differences in IL-1β serum levels (p = 0.543), TNF-α, (p = 0.200) IL-8 (p = 0.107), and IL-10 (p = 0.157) were found. Males had a higher crude incidence of MOF and an 11-fold higher independent risk of MOF. CONCLUSIONS: Persistently elevated IL-6 levels in males are associated with a higher rate of MOF. It is not known if this excessive IL-6 expression in males is causal or only a marker for poor outcome. Further studies are required to elucidate if this early, persistent IL-6 expression is responsible for the gender-based differential outcomes after injury.

AB - OBJECTIVE: An important and persistent laboratory finding has been that males and females respond differently after traumatic injury and hemorrhagic shock. We have previously presented clinical data showing that male gender is independently associated with a 40% higher rate of multiple organ failure (MOF) and a 25% higher rate of nosocomial infection (NI) after injury; however, the mechanism responsible for this dimorphic response after injury has not been adequately characterized clinically. METHODS: Data were obtained from a multicenter prospective cohort study evaluating clinical outcomes in severely injured adults with blunt hemorrhagic shock. Proteomic analysis of serum inflammatory cytokines, on days 0, 1, and 4 postinjury, was performed on 46 males and 34 females. Repeated measures ANOVA were used to compare serial IL-1β, TNF-α, IL-6, IL-8, and IL-10 serum levels across gender, while controlling for important confounders. Logistic regression modeling was then used to analyze the independent risk of MOF and NI associated with gender. RESULTS: IL-6 serum levels were statistically higher in males relative to females (p = 0.008). This higher level of IL-6 expression in males remained statistically significant over time even after controlling for differences in age, initial base deficit, ISS, and 12-hour blood transfusion requirements (p = 0.025). No differences in IL-1β serum levels (p = 0.543), TNF-α, (p = 0.200) IL-8 (p = 0.107), and IL-10 (p = 0.157) were found. Males had a higher crude incidence of MOF and an 11-fold higher independent risk of MOF. CONCLUSIONS: Persistently elevated IL-6 levels in males are associated with a higher rate of MOF. It is not known if this excessive IL-6 expression in males is causal or only a marker for poor outcome. Further studies are required to elucidate if this early, persistent IL-6 expression is responsible for the gender-based differential outcomes after injury.

KW - Gender dimorphism

KW - IL-6

KW - Multiple system organ failure

KW - Nosocomial infection

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