Evidence for prostaglandin-producing supressor cells in HCV patients with normal ALT.
Our objective was to verify the presence of prostaglandin-producing suppressor cells in response to hepatitis C virus antigens in peripheral blood mononuclear cells proliferation. Standard proliferation tests were performed in 31 patients: 20 with chronic hepatitis C after antiviral treatment [7 long-term responders (LTR), 7 relapsers (RR), 6 nonresponders (NR)], 7 with HCV infection with persistently normal aminotransferase levels (PNAL), and 4 with hepatocellular carcinoma. Six antigens were used from the core and NS3 regions. A modified proliferation assay consisting of the addition of indomethacin was also done. Lymphoproliferative responses to the HCV antigens were detectable in 27% (11/41) of test points of LTR, 10% (3/31) of RR, 26% (9/35) of NR, and 18% (7/39) of patients with PNAL. Indomethacin only had effect in PNAL patients, by increasing the frequency of reactivity from 18% (7/39) to 36% (14/39) tests points (P = 0.037); also, in three of these patients (43%) indomethacin strongly modified proliferation to core 31-50 and NS3 1248-1261 antigens, increasing both the frequency and stimulation index from 33% (6/18) to 72% (13/18) (chi2 = 5.43, P = 0.019) and 1.89 +/- 0.43 to 6.18 +/- 4.74 (P = 0.028), respectively. These results suggest that prostaglandin-producing suppressor may play a role in chronic HCV infection by inhibiting cellular immune responses in patients with persistently normal ALT.
Marinho
Rui
R
Liver Unit, Centre of Gastroenterology, Hospital Santa Maria, Medical School of Lisbon, Portugal.
Pinto
Ruth
R
Santos
Maria Livia
ML
de
MouraMiguelCarneiro
M
D000410:Alanine Transaminase / Q000097:blood*; D006528:Carcinoma, Hepatocellular / Q000201:enzymology / Q000276:immunology; D002353:Carrier State / Q000201:enzymology / Q000276:immunology; D015232:Dinoprostone / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D018936:Hepatitis C Antigens / Q000276:immunology; D019698:Hepatitis C, Chronic / Q000188:drug therapy / Q000201:enzymology / Q000276:immunology*; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology; D008099:Liver / Q000201:enzymology; D008113:Liver Neoplasms / Q000201:enzymology / Q000276:immunology; D008213:Lymphocyte Activation; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism
D018936:Hepatitis C Antigens; D000410:Alanine Transaminase; D015232:Dinoprostone; D007213:Indomethacin