PMID- 7664430
OWN - NLM
STAT- MEDLINE
DCOM- 19951012
LR  - 20220408
IS  - 0009-7322 (Print)
IS  - 0009-7322 (Linking)
VI  - 92
IP  - 6
DP  - 1995 Sep 15
TI  - Tumor necrosis factor soluble receptors in patients with various degrees of 
      congestive heart failure.
PG  - 1479-86
AB  - BACKGROUND: Tumor necrosis factor alpha (TNF-alpha) increases in patients with 
      severe congestive heart failure (CHF) and cachexia. Two naturally occurring 
      modulators of TNF-alpha activity have been identified in human serum. These two 
      soluble proteins are the extracellular domains of the TNF receptors (sTNF-RI and 
      sTNF-RII, respectively). The determination of circulating sTNF-Rs could provide 
      us with some additional information about the activation of this cytokine in CHF. 
      METHODS AND RESULTS: This study was undertaken to examine the concentration of 
      sTNF-Rs and of bioactive and antigenic TNF-alpha in 37 consecutive patients with 
      various degrees of CHF compared with that of 26 age-matched healthy subjects. 
      Antigenic TNF-alpha increased (from 14.3 +/- 7.08 to 33.5 +/- 13.1 pg/mL, P < 
      .001) in preterminal patients with severe CHF (New York Heart Association [NYHA] 
      class IV). In these patients, sTNF-Rs were also increased (sTNF-RI from 1.17 +/- 
      0.43 to 4.43 +/- 2.14 ng/mL and sTNF-RII from 2.2 +/- 0.44 to 7.55 +/- 2.28 
      ng/mL, P < .001). When measured by cytolytic bioassay, TNF-alpha was undetectable 
      (< 100 pg/mL). Addition of 625 pg/mL recombinant human TNF-alpha (rhTNF-alpha), 
      corresponding in the bioassay to 60% of the lethal dose, to the serum of healthy 
      subjects resulted in a significant increase of the expected cytotoxicity (from 
      625 to 1290 +/- 411 pg/mL, P < .001). Addition of the same dose of rhTNF-alpha to 
      the serum of patients with mild to moderate CHF (NYHA classes II and III) 
      increased the cytotoxicity from 625 to 877 +/- 132 pg/mL, P < .001. In 4 patients 
      with severe CHF (class IV), the expected cytotoxicity was completely inhibited, 
      whereas it was reduced from 625 to 263 +/- 198 pg/mL, P < .001, in the remaining 
      8 patients. Ten patients died within 1 month of entry into the study. They had 
      the highest level of sTNF-RII (8.18 +/- 1.92 ng/mL). sTNF-RII was a more powerful 
      independent indicator of mortality than TNF-alpha, sTNF-RI, NYHA class, 
      norepinephrine, and atrial natriuretic peptide. CONCLUSIONS: Measurement of 
      sTNF-Rs, in addition to antigenic and bioactive TNF-alpha, is essential for 
      evaluation of the activation of this cytokine in CHF. Both sTNF-Rs increase in 
      preterminal patients with severe CHF and might inhibit the in vitro cytotoxicity 
      of TNF-alpha. Antigenic TNF-alpha also increases in severe CHF. The increased 
      levels of sTNF-RII independently correlate with poor short-term prognosis.
FAU - Ferrari, R
AU  - Ferrari R
AD  - Cattedra di Cardiologia, Universita degli Studi di Brescia, Italy.
FAU - Bachetti, T
AU  - Bachetti T
FAU - Confortini, R
AU  - Confortini R
FAU - Opasich, C
AU  - Opasich C
FAU - Febo, O
AU  - Febo O
FAU - Corti, A
AU  - Corti A
FAU - Cassani, G
AU  - Cassani G
FAU - Visioli, O
AU  - Visioli O
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Circulation
JT  - Circulation
JID - 0147763
RN  - 0 (Receptors, Tumor Necrosis Factor)
RN  - 0 (Tumor Necrosis Factor-alpha)
SB  - IM
CIN - Circulation. 1995 Sep 15;92(6):1379-82. PMID: 7664414
CIN - Circulation. 1996 Sep 1;94(5):1144-6. PMID: 8790067
MH  - Adult
MH  - Female
MH  - Heart Failure/*blood
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Prognosis
MH  - Receptors, Tumor Necrosis Factor/*analysis
MH  - Tumor Necrosis Factor-alpha/analysis/immunology
EDAT- 1995/09/15 00:00
MHDA- 1995/09/15 00:01
CRDT- 1995/09/15 00:00
PHST- 1995/09/15 00:00 [pubmed]
PHST- 1995/09/15 00:01 [medline]
PHST- 1995/09/15 00:00 [entrez]
AID - 10.1161/01.cir.92.6.1479 [doi]
PST - ppublish
SO  - Circulation. 1995 Sep 15;92(6):1479-86. doi: 10.1161/01.cir.92.6.1479.