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Clinical Investigations in Critical Care |

Association Between the TNF-2 Allele and a Better Survival in Cardiogenic Shock*

Olivier Appoloni, MD; Etienne Dupont, MD, PhD; Marleen Vandercruys, RT; Marc Andrien, BS; Jean Duchateau, MD, PhD; Jean-Louis Vincent, MD, PhD, FCCP
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*From the Departments of Intensive Care (Drs. Appoloni and Vincent) and Immunology (Dr. Dupont, Ms. Vandercruys, and Mr. Andrien), Erasme University Hospital, and Department of Immunology (Dr. Duchateau), Brugmann Hospital, Free University of Brussels, Brussels, Belgium.

Correspondence to: Jean-Louis Vincent, MD, PhD, FCCP, Department of Intensive Care, Erasme University Hospital, Route de Lennik 808, B-1070 Brussels, Belgium; e-mail: jlvincen@ulb.ac.be



Chest. 2004;125(6):2232-2237. doi:10.1378/chest.125.6.2232
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Study objectives: Tumor necrosis factor (TNF)-α has been implicated in the pathophysiology of heart failure. We explored a possible association between TNF-α, interleukin (IL)-6, IL-10, transforming growth factor (TGF)-β, and interferon (IFN)-γ cytokine polymorphisms, their in vivo production, and mortality from cardiogenic shock.

Design: Prospective, observational study.

Setting: Thirty-one bed, university, medicosurgical department of intensive care.

Patients: Thirty-three adult patients with cardiogenic shock of recent (< 4 h) onset.

Interventions: None.

Measurements and results: TNF-α, IL-6, IL-10, TGF-β1, and IFN-γ plasma levels were measured by enzyme-linked immunosorbent assay. Polymorphisms of TNF-α within the promoter at position –308a→g, IL-6 within the promoter at position –174c→g, IL-10 within the promoter at position –1082a→g/-819t→c and –819t→c/-592a→c, TGF-β1 at codon 10t→c and codon 25c→g, and IFN-γ at intron 1 at position + 874t→a were studied. The 33 patients had a mean (± SD) age of 64 ± 17 years and a mean simplified acute physiology score II of 62.3 ± 15.3. Twenty-three patients (70%) died in the ICU, including 21 of 26 patients (81%) in the TNF-1 group but only 2 of 7 patients (29%) in the TNF-2 group (p = 0.016). There were no significant differences in median plasma TNF-α levels between the TNF-1 and the TNF-2 groups, but TGF-β1 levels were higher in the survivors than in the nonsurvivors (median, 866 pg/mL; range, 384 to 1,966 pg/mL; vs median, 454 pg/mL; range, 167 to 1,266 pg/mL, respectively; p = 0.02). There were no significant differences in TNF-2 polymorphism between the patients with cardiogenic shock and a group of healthy control subjects (7 of 33 patients vs 13 of 48 subjects, respectively; p = 0.61), but IFN-γ polymorphism was less common in the cardiogenic shock group (p = 0.034).

Conclusions: Patients with the TNF-2 allele have no greater risk of cardiogenic shock but a better survival rate when it develops. Different genetic factors appear to influence the risk of development of, and outcome from, cardiogenic shock.

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