Mixed agonistic-antagonistic cytokine response in whole blood from patients undergoing abdominal aortic aneurysm repair

Abstract

Despite consistent development of clinical signs of systemic inflammatory response syndrome (SIRS) and spontaneous release of IL-6 abdominal aortic aneurysm repair produces a state of impaired pro-inflammatory cytokine response upon a subsequent in vitro Gram-negative stimulus. This early impairment of TNF responsiveness seems to correlate with an unfavorable postoperative course.

Regulation of cytokine synthesis in cardiac surgery: Role of extracorporeal circuit and humoral mediators in vivo and in vitro

“…These data concur with previous observations in cardiac surgical patients [8,9]. Similar endotoxin hyporesponsiveness has been described in patients undergoing abdominal aortic aneurysm repair [12], in polytraumatized [13] and septic patients [14], in whom it was related to clinical outcome. Septic patients whose capacity for cytokine production recovered survived, patients whose cytokine production remained depressed did not [14].…”

Modulation of endotoxin-stimulated TNF-α gene expression by ketamine and propofol in cultured human whole blood

“…Although systemic inflammatory response syndrome (SIRS) and uncontrolled hyperinflammation have attracted considerable interest as a pathway mediating multiple organ dysfunction of the surgical patient, recent evidence suggests that an overwhelming release of anti-inflammatory mediators and decreased production of pro-inflammatory mediators, most notably TNF-α, may propagate the development of MOF in the late course of sepsis [3,5,17]. Consistent with this concept, several studies have provided evidence that an impaired release of TNF-α by whole blood obtained from patients on in vitro LPS stimulation is associated with a poor outcome [5,10,17,23], while recovery of the LPS-stimulated TNF-α response is an indicator of survival/recovery in severely septic patients [5,10,23]. Typically, these patients require long-term treatment in intensive care units (ICU) including continuous administration of sedatives and analgesics.…”

“…RNA (5 µg) was dissolved in sample buffer, containing 50% formamide, 2.2 M formaldehyde, 50 mM 3-(N-morpholino) propanesulfonic acid, 2.72 mg saccharose, 34 µg bromophenol blue, 0.55 µg ethidium bromide and separated on 1.2% agarose gels. After transfer of the RNA onto positively charged nylon membranes (Roche Molecular Diagnostics, Mannheim, Germany), RNA was hybridized to a 32 P(dCTP) labeled human TNF-α complementary DNA fragment (kindly provided by Dr. Jean-Pierre Kremer, GSF National Research Center for Environment and Health, Institute of Experimental Hematology, München, Germany) and staining of the ribosomal RNA was used to correct for unequal loading as described previously [23].…”

“…Alterations in the number and function of circulating immunocompetent cells have been reported after major surgery, reflecting some degree of "immune depression" [8,9]. Impairment of leukocyte functions essential for host defense, such as the ability to release oxygen free-radicals or to mount a cytokine response to bacterial stimuli, has been shown to correlate with an unfavourable postoperative outcome [5,23]. However, the relative contributions of surgery and the trauma itself, as opposed to the effects of the anesthetic regimen and the neurohumoral stress response, are difficult to distinguish [2,4,11,16].…”

Endotoxin

“…B. durch IL-6), auch eine antiinflammatorische Wirkung (z. B. durch IL-10),die das frühe proinflammatorische Signal der Makrophagen beendet [22].Ein Überwiegen antiinflammatorischer Zytokine sowie eine fehlende Aktivierbarkeit der Effektorzellen des Immunsystems ist mittlerweile für eine Vielzahl chirurgischer Eingriffe nachgewiesen worden.Sie korreliert mit einem ungünstigen postoperativen Verlauf [26,56]; vermutlich weil die Entstehung nosokomialer Infektionen als maßgeblichem Faktor für die Entwicklung einer Sepsis gefördert wird.…”