Gender Differences in the Inflammatory Response and Survival Following Haemorrhage and Subsequent Sepsis

Diodato, Michael D.; Knöferl, Markus W.; Schwacha, Martin G.; Bland, Kirby I.; Chaudry, Irshad H.

doi:10.1006/cyto.2001.0861

Cited by 229 publications

(162 citation statements)

References 46 publications

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“…Our findings are consistent with previous reports indicating a lower rate of sepsis and severe sepsis as well as sepsis-related mortality in females than males [1,4,16,52]. The sex discrepancy in development and outcome of infection and sepsis can be partly explained by the action of sex hormones on immune system function.…”

Section: Discussionsupporting

confidence: 93%

Has the Rate of In-hospital Infections After Total Joint Arthroplasty Decreased?

Rasouli

Maltenfort

Purtill

et al. 2013

Clinical Orthopaedics &Amp; Related Research

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Background Although infections are a major cause of morbidity and mortality after total joint arthroplasty (TJA), little is known about nationwide epidemiology and trends of infections after TJA. Questions/purposes We therefore determined (1) trends of postoperative pneumonia, urinary tract infection (UTI), surgical site infection (SSI), sepsis, and severe sepsis after TJA; (2) risk factors of these infections; (3) effect of these infections on length of stay (LOS) and hospital charges; and (4) the infection-related mortality rate and its predictors. Methods The International Classification of Diseases, 9 th Revision codes were used to identify patients who underwent TJA and were diagnosed with aforementioned infections during hospitalization in the Nationwide Inpatient Sample database from 2002 to 2010. Multivariate analysis was performed to identify risk factors of these infections. Results Rates of pneumonia, UTI, SSI, sepsis, and severe sepsis were 0.74%, 3.26%, 0.31%, 0.25%, and 0.15%, respectively. Number of comorbidities and type of TJA were independent predictors of infection. Mortality decreased during the study period (odds ratio, 0.87; 95% confidence interval, 0.86-0.89). The median LOS was 3 days without complications but increased in the presence of SSI (median, 7 days), sepsis (median, 12 days), and severe sepsis (median, 15 days). Occurrence of pneumonia, sepsis, and severe sepsis increased risk of mortality 5.2, 8.5, and 66.2 times, respectively. Conclusions Rates of UTI, pneumonia, and SSI but not sepsis and severe sepsis are apparently decreasing. The likelihood of infection is increasing with number of comorbidities and revision surgeries. Rate of sepsis-related mortality is also decreasing. Level of Evidence Level II, prognostic study. See Guidelines for Authors for a complete description of levels of evidence.

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Section: Discussionsupporting

confidence: 93%

Has the Rate of In-hospital Infections After Total Joint Arthroplasty Decreased?

Rasouli

Maltenfort

Purtill

et al. 2013

Clinical Orthopaedics &Amp; Related Research

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“…In addition, experimental studies indicate that proestrus females maintain immune function after trauma-hemorrhage, whereas males do not (3). The maintained immune functional capacity of females under such conditions also correlates with a decreased mortality from subsequent sepsis (16). Studies also indicate that, after trauma-hemorrhage, the immunoprotected state in proestrus females is estrogen mediated, whereas the immunosuppressed state in males is androgen mediated (3).…”

mentioning

confidence: 99%

Androgen-mediated modulation of macrophage function after trauma-hemorrhage: central role of 5α-dihydrotestosterone

Schneider

Schwacha

Samy

et al. 2003

Journal of Applied Physiology

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Androgens have been implicated as the causative factor for the postinjury immune dysfunction in males; however, it remains unknown whether androgens directly affect macrophages. To study this, male mice were sham operated or subjected to trauma (i.e., midline laparotomy) and hemorrhagic shock (mean arterial pressure, 30 ± 5 mmHg for 90 min and then resuscitated). The mice received the 5α-reductase inhibitor 4-hydroxyandrostenedione (4-OHA) before resuscitation. Plasma TNF-α, IL-6, and IL-10 levels were elevated after trauma-hemorrhage and normalized by 4-OHA. TNF-α and IL-6 production by splenic macrophages was decreased after injury, whereas Kupffer cell production of these mediators was enhanced. 4-OHA normalized cytokine production. Androgens suppressed cytokine production by splenic macrophages from hemorrhaged mice, whereas it enhanced TNF-α and IL-6 production by Kupffer cells. The addition of 4-OHA in vitro normalized cytokine production by cells treated with testosterone, but it had no effect on dihydrotestosterone-treated cells. These results indicate that androgens directly affect macrophage function in males after trauma and hemorrhagic shock and that the intracellular conversion of testosterone to dihydrotestosterone is of particular importance in mediating the androgen-induced effects.

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“…Furthermore, proestrus females are more resistant to subsequent sepsis than male mice and had a significantly lower mortality following trauma-hemorrhage and sepsis [1;29]. Our previous studies showed that administration of a single dose of E2 following trauma-hemorrhage improved macrophage and lymphocyte functions [29]. However, blockade of ER abolished the salutary effects of 17β-estradiol [30], suggesting that the salutary effects of 17β-estradiol are mediated via ER.…”

Section: Discussionmentioning

confidence: 99%

Mitogen activated protein kinase (MAPK) mediates non-genomic pathway of estrogen on T cell cytokine production following trauma-hemorrhage

Suzuki

Hsieh

et al. 2008

Cytokine

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Although studies have shown 17β-estradiol (E2) administration following trauma-hemorrhage (T-H) attenuates alterations in T cell cytokine production, it remains unknown whether such effects of E2 are mediated via genomic or non-genomic pathways. In this study, we determined the nongenomic effects of E2 on splenic T cell cytokine production and the role of MAPK following T-H. Male Sprague-Dawley rats underwent T-H (mean BP 40 mmHg for 90 min, then resuscitation). E2, E2 conjugated with BSA (E2-BSA, 1 mg/kg E2) with or without an estrogen receptor antagonist (ICI 182 780), or vehicle was administrated during resuscitation. Two hrs thereafter, T cell production of IL-2 and IFN-γ and activation of MAPK (p38, ERK-1/2 and JNK) were determined. The effect of selective MAPK inhibitors on cytokine production was also examined in vitro. IL-2 and IFN-γ production capacity and MAPK activation decreased in T cells following T-H. However, E2 administration normalized these parameters. Although E2-BSA administration also attenuated suppression in cytokine production, the values were lower compared to sham. In contrast, E2-BSA prevented T-H-induced suppression in MAPK activation to the same extent as E2. Co-administration of ICI 182 780 abolished E2-BSA effects. These findings suggest E2 effects on T cell cytokine production following T-H are mediated at least in part via non-genomic pathway and these nongenomic effects are likely mediated via MAPK pathways.

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Gender Differences in the Inflammatory Response and Survival Following Haemorrhage and Subsequent Sepsis

Cited by 229 publications

References 46 publications

Has the Rate of In-hospital Infections After Total Joint Arthroplasty Decreased?

Has the Rate of In-hospital Infections After Total Joint Arthroplasty Decreased?

Androgen-mediated modulation of macrophage function after trauma-hemorrhage: central role of 5α-dihydrotestosterone

Mitogen activated protein kinase (MAPK) mediates non-genomic pathway of estrogen on T cell cytokine production following trauma-hemorrhage

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