Study objectives: Tumor necrosis factor (TNF)-alpha has been implicated in the pathophysiology of heart failure. We explored a possible association between TNF-alpha, interleukin (IL)-6, IL-10, transforming growth factor (TGF)-beta, and interferon (IFN)-gamma 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-alpha, IL-6, IL-10, TGF-beta1, and IFN-gamma plasma levels were measured by enzyme-linked immunosorbent assay. Polymorphisms of TNF-alpha 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-beta1 at codon 10t-->c and codon 25c-->g, and IFN-gamma 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-alpha levels between the TNF-1 and the TNF-2 groups, but TGF-beta1 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-gamma 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.