title: Relationship between age/gender-induced survival changes and the magnitude of inflammatory activation and organ dysfunction in post-traumatic sepsis.
abstract: Age/gender may likely influence the course of septic complications after trauma. We aimed to characterize the influence of age/gender on the response of circulating cytokines, cells and organ function in post-traumatic sepsis. We additionally tested whether post-traumatic responses alone can accurately predict outcomes in subsequent post-traumatic sepsis. A mouse 2-hit model of trauma/hemorrhage (TH, 1(st) hit) and cecal ligation and puncture (CLP, 2(nd) hit) was employed. 3, 15 and 20 month (m) old female (♀) and male (♂) CD-1 mice underwent sublethal TH followed by CLP 2 days later. Blood was sampled daily until day 6 post-TH and survival was followed for 16 days. To compare general response patterns among groups, we calculated two scores: the inflammatory response (including KC, MIP-1α, TNFα, MCP-1, IFNγ, IL-1β,-5,-6,-10) and the organ dysfunction score (Urea, ALT, AST and LDH). Moreover, mice were retrospectively divided into survivors (SUR) and dying (DIE) based on post-CLP outcome. In general, females survived better than males and their survival did not correspond to any specific estrus cycle phase. Pre-CLP phase: the post-TH inflammatory score was weakest in 3 m♂ but there were no changes among remaining groups (similar lack of differences in the organ dysfunction score). TH induced a 40% increase of IFNγ, MIP-1α and IL-5 in 15 m♂ SUR (vs. DIE) but predictive accuracy for post-CLP outcomes was moderate. Post-CLP phase: while stable in males, inflammatory response score in 15 m and 20 m females decreased with age at day 1 and 2 post-CLP. SUR vs. DIE differences in inflammatory and organ dysfunction score were evident but their magnitude was comparable across age/gender. Nearly identical activation of the humoral inflammatory and organ function compartments, both across groups and according to sepsis severity, suggests that they are not directly responsible for the age/gender-dependent disparity in TH-CLP survival in the studied young-to-mature population.
authors.affiliation: Ludwig Boltzmann Institute for Experimental and Clinical Traumatology in the Trauma Research Center of Allgemeine Unfallversicherungsanstalt, Vienna, Austria.
authors.forename: Susanne
authors.initials: S
authors.lastname: Drechsler
authors.forename: Katrin
authors.initials: K
authors.lastname: Weixelbaumer
authors.forename: Pierre
authors.initials: P
authors.lastname: Raeven
authors.forename: Mohammad
authors.initials: M
authors.lastname: Jafarmadar
authors.forename: Anna
authors.initials: A
authors.lastname: Khadem
authors.forename: Martijn
authors.initials: M
authors.lastname: van Griensven
authors.forename: Soheyl
authors.initials: S
authors.lastname: Bahrami
authors.forename: Marcin Filip
authors.initials: MF
authors.lastname: Osuchowski
mesh_terms: D000375:Aging / Q000473:pathology*; D000818:Animals; D002432:Cecum / Q000503:physiopathology; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D030762:Estrous Cycle; D005260:Female; D006470:Hemorrhage / Q000150:complications; D006801:Humans; D007249:Inflammation / Q000209:etiology* / Q000503:physiopathology*; D008297:Male; D051379:Mice; D008954:Models, Biological; D011677:Punctures; D018805:Sepsis / Q000209:etiology* / Q000503:physiopathology*; D012727:Sex Characteristics; D016019:Survival Analysis; D014947:Wounds and Injuries / Q000150:complications* / Q000503:physiopathology
chemical_list: D016207:Cytokines