Gender differences in sepsis

Figures & data

Figure 1. Schematic illustration of the effect of gender on cardiovascular performance and cellular immunity following trauma and severe blood loss.

Table 1. Effect of sex steroids/agents on immune/cardiovascular responses following injury/sepsis in murine models and humans

Author	Reference	Species	Model	Agent	Effect
Angele et al.,1997	59	Murine male C3H/HeN mice	Hemorrhage, sepsis	Testosterone receptor blockade (flutamide)	Splenocyte proliferation ↑, IL-2 ↑, splenic macrophage IL-1,6 ↑, survival ↑
Yu et al., 2005	34	Murine male Sprague–Dawley rats	Trauma, hemorrhage, cardiac function	Testosterone receptor blockade (flutamide)	Cardiac output ↑, estrogen receptors in cardiomyocytes ↑
Lin et al., 2012	61	Murine inbred male mice	Heatstroke	Testosterone receptor blockade (flutamide)	Systemic inflammation ↓, survival ↑, apoptosis ↓
Barkhausen et al., 2009	64	Murine male NMRI mice	Hemorrhage, sepsis	DHEA	Survival ↑, restoration of TNF-α mRNA expression in lung and liver
Frantz et al., 2005	68	Human	PBMCs from patients undergoing abdominal surgery	DHEA	Proinflammatory cytokine release ↑ (TNF-α, IL-6, IL-1β)
Shimizu et al., 2004	70	Murine Sprague–Dawley rats	Trauma, hemorrhage	Androstenediol/DHEA	Cardiac function ↑, splanchnic perfusion ↑, inflammatory response (IL-6) ↓
Kiang et al., 2007	71	Murine Sprague–Dawley rats	Trauma, hemorrhage	Androstenediol/DHEA	Apoptosis ↓ via caspase 3 ↓, iNOS ↓
Gonzalez-Rey et al., 2009	74	Human/murine	Experimental colitis	Female human MSCs	Restoration of immune functions, overwhelming inflammatory response ↓ (TNF-α, IFN-γ, IL-6, IL-1β, IL-12)
Nemeth et al., 2009	77	Human/murine	Experimental sepsis	Female human MSCs	Survival and organ function ↑, inflammation ↓ via macrophage derived IL-10

Angele MK, Wichmann MW, Ayala A, Cioffi WG, Chaudry IH. Testosterone receptor blockade after hemorrhage in males. Restoration of the depressed immune functions and improved survival following subsequent sepsis. Arch Surg 1997; 132:1207 - 14; http://dx.doi.org/10.1001/archsurg.1997.01430350057010; PMID: 9366714

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Yu HP, Yang S, Choudhry MA, Hsieh YC, Bland KI, Chaudry IH. Mechanism responsible for the salutary effects of flutamide on cardiac performance after trauma-hemorrhagic shock: Upregulation of cardiomyocyte estrogen receptors. Surgery 2005; 138:85 - 92; http://dx.doi.org/10.1016/j.surg.2005.03.006; PMID: 16003321

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Lin CY, Hsu CC, Lin MT, Chen SH. Flutamide, an androgen receptor antagonist, improves heatstroke outcomes in mice. Eur J Pharmacol 2012; 688:62 - 7; http://dx.doi.org/10.1016/j.ejphar.2012.05.002; PMID: 22609231

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Barkhausen T, Hildebrand F, Krettek C, van Griensven M. DHEA-dependent and organ-specific regulation of TNF-alpha mRNA expression in a murine polymicrobial sepsis and trauma model. Crit Care 2009; 13:R114; http://dx.doi.org/10.1186/cc7963; PMID: 19594900

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Frantz MC, Prix NJ, Wichmann MW, van den Engel NK, Hernandez-Richter T, Faist E, Chaudry IH, Jauch KW, Angele MK. Dehydroepiandrosterone restores depressed peripheral blood mononuclear cell function following major abdominal surgery via the estrogen receptors. Crit Care Med 2005; 33:1779 - 86; http://dx.doi.org/10.1097/01.CCM.0000172278.91959.38; PMID: 16096456

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Shimizu T, Choudhry MA, Szalay L. Rue LW3, Bland KI, Chaudry IH. Salutary effects of androstenediol on cardiac function and splanchnic perfusion after trauma-hemorrhage. Am J Physiol Regul Integr Comp Physiol 2004; 287:386 - 90; http://dx.doi.org/10.1152/ajpregu.00214.2004

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Kiang JG, Peckham RM, Duke LE, Shimizu T, Chaudry IH, Tsokos GC. Androstenediol inhibits the trauma-hemorrhage-induced increase in caspase-3 by downregulating the inducible nitric oxide synthase pathway. J Appl Physiol (1985) 2007; 102:933 - 41; http://dx.doi.org/10.1152/japplphysiol.00919.2006; PMID: 17110508

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Gonzalez-Rey E, Anderson P, González MA, Rico L, Büscher D, Delgado M. Human adult stem cells derived from adipose tissue protect against experimental colitis and sepsis. Gut 2009; 58:929 - 39; http://dx.doi.org/10.1136/gut.2008.168534; PMID: 19136511

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Németh K, Leelahavanichkul A, Yuen PS, Mayer B, Parmelee A, Doi K, Robey PG, Leelahavanichkul K, Koller BH, Brown JM, et al. Bone marrow stromal cells attenuate sepsis via prostaglandin E(2)-dependent reprogramming of host macrophages to increase their interleukin-10 production. Nat Med 2009; 15:42 - 9; http://dx.doi.org/10.1038/nm.1905; PMID: 19098906

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