PMID- 9440625
OWN - NLM
STAT- MEDLINE
DCOM- 19980217
LR  - 20220409
IS  - 0163-2116 (Print)
IS  - 0163-2116 (Linking)
VI  - 42
IP  - 12
DP  - 1997 Dec
TI  - Activation of tumor necrosis factor-alpha system in chronic hepatitis C virus 
      infection.
PG  - 2487-94
AB  - Tumor necrosis factor-alpha (TNF-alpha) plays a central role in the host's 
      immunomodulatory response to infective agents. To evaluate the TNF-alpha system 
      in patients with chronic hepatitis C virus (HCV) infection, plasma, serum, and 
      peripheral blood mononuclear cells (PBMC) were prospectively collected from 53 
      patients and 33 healthy control subjects. Circulating TNF-alpha and TNF receptors 
      were assayed by their respective enzyme immunoassays. In addition, TNF-alpha mRNA 
      was quantitated in PBMC using a branched DNA assay, and production of TNF-alpha 
      by PBMC with and without lipopolysaccharide was also assessed. Patients with 
      chronic HCV infection had a higher level of circulating TNF-alpha compared to 
      healthy control subjects (9.62 +/- 6.01 vs 3.66 +/- 1.23 pg/ml, P < 0.001). They 
      also had higher circulating levels of TNF receptors compared to control (CD120a: 
      3323 +/- 1267, pg/ml, N = 49 vs 1855 +/- 422 pg/ml, N = 33, P < 0.001; CD120b: 
      1290 +/- 650 pg/ml, N = 51, vs 863 +/- 207 pg/ml, N = 33, P < 0.001). Plasma 
      TNF-alpha level correlated with circulating CD120a (r = 0.52, N = 49, P < 0.001) 
      and weakly with CD120b (r = 0.32, N = 51, P = 0.02). Plasma TNF-alpha also 
      correlated with markers of hepatocellular injury, including ALT (r = 0.34, N = 
      53, P = 0.01) and alpha-GST (r = 0.31, N = 43, P = 0.042), but not with serum HCV 
      RNA levels. There was no difference in the TNF-alpha mRNA levels in PBMC between 
      patients with chronic HCV infection (1.4 +/- 1.9 units/10[6] cells, N = 8) and 
      healthy control subjects (2.1 +/- 1.4 units/10[6] cells, N = 8, P = NS). There 
      was also no difference in the spontaneous production of TNF-alpha by PBMC (1 x 
      10[6] cells/ml) between patients with chronic HCV infection (14.2 +/- 36.5 pg/ml, 
      N = 11) and healthy subjects (11.9 +/- 14.0 pg/ml, N = 14, P = NS). However, 
      patients with chronic HCV infection produced more TNF-alpha upon stimulation with 
      lipopolysaccharide compared to healthy control subjects (1278 +/- 693 pg/ml, N = 
      11, vs 629 +/- 689 pg/ml, N = 14, P < 0.05). These data indicate that the 
      TNF-alpha system is activated in patients with chronic HCV infection.
FAU - Nelson, D R
AU  - Nelson DR
AD  - Department of Medicine, University of Florida, Gainesville, USA.
FAU - Lim, H L
AU  - Lim HL
FAU - Marousis, C G
AU  - Marousis CG
FAU - Fang, J W
AU  - Fang JW
FAU - Davis, G L
AU  - Davis GL
FAU - Shen, L
AU  - Shen L
FAU - Urdea, M S
AU  - Urdea MS
FAU - Kolberg, J A
AU  - Kolberg JA
FAU - Lau, J Y
AU  - Lau JY
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Dig Dis Sci
JT  - Digestive diseases and sciences
JID - 7902782
RN  - 0 (RNA, Messenger)
RN  - 0 (RNA, Viral)
RN  - 0 (Receptors, Tumor Necrosis Factor)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - EC 2.6.1.2 (Alanine Transaminase)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Aged
MH  - Alanine Transaminase/blood
MH  - Female
MH  - Genotype
MH  - Hepacivirus/genetics
MH  - Hepatitis C, Chronic/*immunology/pathology
MH  - Humans
MH  - Leukocytes, Mononuclear/immunology
MH  - Liver/pathology
MH  - Male
MH  - Middle Aged
MH  - RNA, Messenger/analysis
MH  - RNA, Viral/analysis
MH  - Receptors, Tumor Necrosis Factor/analysis
MH  - Tumor Necrosis Factor-alpha/*analysis
EDAT- 1998/01/24 00:00
MHDA- 1998/01/24 00:01
CRDT- 1998/01/24 00:00
PHST- 1998/01/24 00:00 [pubmed]
PHST- 1998/01/24 00:01 [medline]
PHST- 1998/01/24 00:00 [entrez]
AID - 10.1023/a:1018804426724 [doi]
PST - ppublish
SO  - Dig Dis Sci. 1997 Dec;42(12):2487-94. doi: 10.1023/a:1018804426724.