Effects of interferon and ribavirin combination therapy on CD4+ proliferation, lymphocyte activation, and Th1 and Th2 cytokine profiles in chronic hepatitis C
We studied the relationship between immunological markers such as CD4+ proliferation, cytokines profile and lymphocyte activation markers in patients with chronic hepatitis C, having different responses to interferon (IFN) and ribavirin (RBV) treatment. A prospective study of 20 patients was conduct...
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| Veröffentlicht in: | Journal of viral hepatitis 2004-05, Vol.11 (3), p.206-216 |
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| creator | Marinho, R. T. Pinto, R. Santos, M. L. Lobos, I. V. Moura, M. C. |
| description | We studied the relationship between immunological markers such as CD4+ proliferation, cytokines profile and lymphocyte activation markers in patients with chronic hepatitis C, having different responses to interferon (IFN) and ribavirin (RBV) treatment. A prospective study of 20 patients was conducted, six had received IFN‐alpha‐2b alone and 14 IFN in combination with RBV.
The proliferative immune responses of peripheral blood mononuclear cells to hepatitis C virus peptides and the lymphocyte activation markers (CD25+, CD38+ and CD69+) were assessed before treatment, at 1 week, and 1, 3 and 6 months of treatment. Cytokines interleukin (IL)‐2, IFN‐γ, IL‐4 and IL‐10 were determined in supernatants before onset of treatment and at 1 and 6 months thereafter.
Stimulation indices (SI) were higher in the sustained responders (SR), in comparison with those with no response (NR), before treatment (5.2 ± 3.7 to 3.3 ± 1.9, P = 0.028) and also at 6 months (7.8 ± 1.9 to 4.1 ± 1.2, P = 0.021). Patients with SR also had high SI to NS3 when compared with those with transitory response or no response (NR) (4.9 ± 2.5 and 3.3 ± 1.1, P = 0.033). At 1 month, SR had higher supernatant IL‐2 than those with NR (133.8 ± 119.2 to 56.0 ± 89.3 pg/mL, P = 0.023) and lower levels of IL‐10 (13.8 ± 10.1 and 167.1 ± 272.0 pg/mL, P = 0.023) in response to NS3. Combination therapy induced a higher percentage of the lymphocyte activation markers CD69+ and CD38+.
In conclusion, we found that SR is associated with higher CD4+ proliferation particularly in response to the NS3 region, promoting a T‐helper (Th)1/Th0 profile of cytokines, and that combination therapy induced a higher percentage of lymphocyte activation than therapy with IFN alone. |
| doi_str_mv | 10.1111/j.1365-2893.2004.00496.x |
| format | Article |
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The proliferative immune responses of peripheral blood mononuclear cells to hepatitis C virus peptides and the lymphocyte activation markers (CD25+, CD38+ and CD69+) were assessed before treatment, at 1 week, and 1, 3 and 6 months of treatment. Cytokines interleukin (IL)‐2, IFN‐γ, IL‐4 and IL‐10 were determined in supernatants before onset of treatment and at 1 and 6 months thereafter.
Stimulation indices (SI) were higher in the sustained responders (SR), in comparison with those with no response (NR), before treatment (5.2 ± 3.7 to 3.3 ± 1.9, P = 0.028) and also at 6 months (7.8 ± 1.9 to 4.1 ± 1.2, P = 0.021). Patients with SR also had high SI to NS3 when compared with those with transitory response or no response (NR) (4.9 ± 2.5 and 3.3 ± 1.1, P = 0.033). At 1 month, SR had higher supernatant IL‐2 than those with NR (133.8 ± 119.2 to 56.0 ± 89.3 pg/mL, P = 0.023) and lower levels of IL‐10 (13.8 ± 10.1 and 167.1 ± 272.0 pg/mL, P = 0.023) in response to NS3. Combination therapy induced a higher percentage of the lymphocyte activation markers CD69+ and CD38+.
In conclusion, we found that SR is associated with higher CD4+ proliferation particularly in response to the NS3 region, promoting a T‐helper (Th)1/Th0 profile of cytokines, and that combination therapy induced a higher percentage of lymphocyte activation than therapy with IFN alone.</description><identifier>ISSN: 1352-0504</identifier><identifier>EISSN: 1365-2893</identifier><identifier>DOI: 10.1111/j.1365-2893.2004.00496.x</identifier><identifier>PMID: 15117322</identifier><language>eng</language><publisher>Oxford, UK: Blackwell Science Ltd</publisher><subject>Adult ; Antiviral Agents - administration & dosage ; Case-Control Studies ; CD4-positive ; CD4-Positive T-Lymphocytes - drug effects ; CD4-Positive T-Lymphocytes - immunology ; CD4-Positive T-Lymphocytes - pathology ; Cell Division - drug effects ; cytokines ; Cytokines - metabolism ; Drug Therapy, Combination ; Female ; hepatitis C ; Hepatitis C virus ; Hepatitis C, Chronic - drug therapy ; Hepatitis C, Chronic - immunology ; Humans ; In Vitro Techniques ; interferon-alpha ; Interferon-alpha - administration & dosage ; lymphocyte activation ; Lymphocyte Activation - drug effects ; Male ; Middle Aged ; Prospective Studies ; Recombinant Proteins ; ribavirin ; Ribavirin - administration & dosage ; T lymphocytes ; Th1 Cells - drug effects ; Th1 Cells - immunology ; Th2 Cells - drug effects ; Th2 Cells - immunology ; Viremia - drug therapy ; Viremia - immunology</subject><ispartof>Journal of viral hepatitis, 2004-05, Vol.11 (3), p.206-216</ispartof><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4996-5fcd21cbb9fe8a48c0a7209ff6941a6f29d900574896d5e7792d9cca595ba673</citedby><cites>FETCH-LOGICAL-c4996-5fcd21cbb9fe8a48c0a7209ff6941a6f29d900574896d5e7792d9cca595ba673</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1111%2Fj.1365-2893.2004.00496.x$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1111%2Fj.1365-2893.2004.00496.x$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,777,781,1412,27905,27906,45555,45556</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/15117322$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Marinho, R. T.</creatorcontrib><creatorcontrib>Pinto, R.</creatorcontrib><creatorcontrib>Santos, M. L.</creatorcontrib><creatorcontrib>Lobos, I. V.</creatorcontrib><creatorcontrib>Moura, M. C.</creatorcontrib><title>Effects of interferon and ribavirin combination therapy on CD4+ proliferation, lymphocyte activation, and Th1 and Th2 cytokine profiles in chronic hepatitis C</title><title>Journal of viral hepatitis</title><addtitle>J Viral Hepat</addtitle><description>We studied the relationship between immunological markers such as CD4+ proliferation, cytokines profile and lymphocyte activation markers in patients with chronic hepatitis C, having different responses to interferon (IFN) and ribavirin (RBV) treatment. A prospective study of 20 patients was conducted, six had received IFN‐alpha‐2b alone and 14 IFN in combination with RBV.
The proliferative immune responses of peripheral blood mononuclear cells to hepatitis C virus peptides and the lymphocyte activation markers (CD25+, CD38+ and CD69+) were assessed before treatment, at 1 week, and 1, 3 and 6 months of treatment. Cytokines interleukin (IL)‐2, IFN‐γ, IL‐4 and IL‐10 were determined in supernatants before onset of treatment and at 1 and 6 months thereafter.
Stimulation indices (SI) were higher in the sustained responders (SR), in comparison with those with no response (NR), before treatment (5.2 ± 3.7 to 3.3 ± 1.9, P = 0.028) and also at 6 months (7.8 ± 1.9 to 4.1 ± 1.2, P = 0.021). Patients with SR also had high SI to NS3 when compared with those with transitory response or no response (NR) (4.9 ± 2.5 and 3.3 ± 1.1, P = 0.033). At 1 month, SR had higher supernatant IL‐2 than those with NR (133.8 ± 119.2 to 56.0 ± 89.3 pg/mL, P = 0.023) and lower levels of IL‐10 (13.8 ± 10.1 and 167.1 ± 272.0 pg/mL, P = 0.023) in response to NS3. Combination therapy induced a higher percentage of the lymphocyte activation markers CD69+ and CD38+.
In conclusion, we found that SR is associated with higher CD4+ proliferation particularly in response to the NS3 region, promoting a T‐helper (Th)1/Th0 profile of cytokines, and that combination therapy induced a higher percentage of lymphocyte activation than therapy with IFN alone.</description><subject>Adult</subject><subject>Antiviral Agents - administration & dosage</subject><subject>Case-Control Studies</subject><subject>CD4-positive</subject><subject>CD4-Positive T-Lymphocytes - drug effects</subject><subject>CD4-Positive T-Lymphocytes - immunology</subject><subject>CD4-Positive T-Lymphocytes - pathology</subject><subject>Cell Division - drug effects</subject><subject>cytokines</subject><subject>Cytokines - metabolism</subject><subject>Drug Therapy, Combination</subject><subject>Female</subject><subject>hepatitis C</subject><subject>Hepatitis C virus</subject><subject>Hepatitis C, Chronic - drug therapy</subject><subject>Hepatitis C, Chronic - immunology</subject><subject>Humans</subject><subject>In Vitro Techniques</subject><subject>interferon-alpha</subject><subject>Interferon-alpha - administration & dosage</subject><subject>lymphocyte activation</subject><subject>Lymphocyte Activation - drug effects</subject><subject>Male</subject><subject>Middle Aged</subject><subject>Prospective Studies</subject><subject>Recombinant Proteins</subject><subject>ribavirin</subject><subject>Ribavirin - administration & dosage</subject><subject>T lymphocytes</subject><subject>Th1 Cells - drug effects</subject><subject>Th1 Cells - immunology</subject><subject>Th2 Cells - drug effects</subject><subject>Th2 Cells - immunology</subject><subject>Viremia - drug therapy</subject><subject>Viremia - immunology</subject><issn>1352-0504</issn><issn>1365-2893</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2004</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNkc9u1DAQxi0EoqXwCsgnLpDUduw4lrigUFqqtkhoBRIXy3Fsxdv8q50tm5fhWXG6UTlSS9aMPN9vxpoPAIhRiuM53aY4y1lCCpGlBCGaxivydP8MHD8Wni85IwliiB6BVyFsEcIZYfglOMIMY54Rcgz-nFlr9BTgYKHrJ-Ot8UMPVV9D7yp177zroR66yvVqcrEyNcarcYYxLT_T93D0Q-si9FD9ANu5G5tBz5OBSk_ufn1e-m0avEYCo2C4db1ZcOtaE-AypomjnYaNGSM2uQDL1-CFVW0wb9Z4AjZfzjblRXL17fxr-ekq0VSIPGFW1wTrqhLWFIoWGilOkLA2FxSr3BJRC4QYp4XIa2Y4F6QWWismWKVynp2Ad4e28Tt3OxMm2bmgTduq3gy7IDmOC83y4r9CzIVgtMBRWByE2g8heGPl6F2n_CwxkouHcisXq-RilVw8lA8eyn1E364zdlVn6n_galoUfDwIfsfNzU9uLC9_XMQk4skBd2Ey-0dc-VsZV8GZ_HlzLovv1zf0V8klyf4CGSS7nQ</recordid><startdate>200405</startdate><enddate>200405</enddate><creator>Marinho, R. T.</creator><creator>Pinto, R.</creator><creator>Santos, M. L.</creator><creator>Lobos, I. V.</creator><creator>Moura, M. C.</creator><general>Blackwell Science Ltd</general><scope>BSCLL</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7U9</scope><scope>H94</scope><scope>7X8</scope></search><sort><creationdate>200405</creationdate><title>Effects of interferon and ribavirin combination therapy on CD4+ proliferation, lymphocyte activation, and Th1 and Th2 cytokine profiles in chronic hepatitis C</title><author>Marinho, R. T. ; Pinto, R. ; Santos, M. L. ; Lobos, I. V. ; Moura, M. 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T.</creatorcontrib><creatorcontrib>Pinto, R.</creatorcontrib><creatorcontrib>Santos, M. L.</creatorcontrib><creatorcontrib>Lobos, I. V.</creatorcontrib><creatorcontrib>Moura, M. C.</creatorcontrib><collection>Istex</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Virology and AIDS Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Journal of viral hepatitis</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Marinho, R. T.</au><au>Pinto, R.</au><au>Santos, M. L.</au><au>Lobos, I. V.</au><au>Moura, M. C.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Effects of interferon and ribavirin combination therapy on CD4+ proliferation, lymphocyte activation, and Th1 and Th2 cytokine profiles in chronic hepatitis C</atitle><jtitle>Journal of viral hepatitis</jtitle><addtitle>J Viral Hepat</addtitle><date>2004-05</date><risdate>2004</risdate><volume>11</volume><issue>3</issue><spage>206</spage><epage>216</epage><pages>206-216</pages><issn>1352-0504</issn><eissn>1365-2893</eissn><abstract>We studied the relationship between immunological markers such as CD4+ proliferation, cytokines profile and lymphocyte activation markers in patients with chronic hepatitis C, having different responses to interferon (IFN) and ribavirin (RBV) treatment. A prospective study of 20 patients was conducted, six had received IFN‐alpha‐2b alone and 14 IFN in combination with RBV.
The proliferative immune responses of peripheral blood mononuclear cells to hepatitis C virus peptides and the lymphocyte activation markers (CD25+, CD38+ and CD69+) were assessed before treatment, at 1 week, and 1, 3 and 6 months of treatment. Cytokines interleukin (IL)‐2, IFN‐γ, IL‐4 and IL‐10 were determined in supernatants before onset of treatment and at 1 and 6 months thereafter.
Stimulation indices (SI) were higher in the sustained responders (SR), in comparison with those with no response (NR), before treatment (5.2 ± 3.7 to 3.3 ± 1.9, P = 0.028) and also at 6 months (7.8 ± 1.9 to 4.1 ± 1.2, P = 0.021). Patients with SR also had high SI to NS3 when compared with those with transitory response or no response (NR) (4.9 ± 2.5 and 3.3 ± 1.1, P = 0.033). At 1 month, SR had higher supernatant IL‐2 than those with NR (133.8 ± 119.2 to 56.0 ± 89.3 pg/mL, P = 0.023) and lower levels of IL‐10 (13.8 ± 10.1 and 167.1 ± 272.0 pg/mL, P = 0.023) in response to NS3. Combination therapy induced a higher percentage of the lymphocyte activation markers CD69+ and CD38+.
In conclusion, we found that SR is associated with higher CD4+ proliferation particularly in response to the NS3 region, promoting a T‐helper (Th)1/Th0 profile of cytokines, and that combination therapy induced a higher percentage of lymphocyte activation than therapy with IFN alone.</abstract><cop>Oxford, UK</cop><pub>Blackwell Science Ltd</pub><pmid>15117322</pmid><doi>10.1111/j.1365-2893.2004.00496.x</doi><tpages>11</tpages></addata></record> |
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| subjects | Adult Antiviral Agents - administration & dosage Case-Control Studies CD4-positive CD4-Positive T-Lymphocytes - drug effects CD4-Positive T-Lymphocytes - immunology CD4-Positive T-Lymphocytes - pathology Cell Division - drug effects cytokines Cytokines - metabolism Drug Therapy, Combination Female hepatitis C Hepatitis C virus Hepatitis C, Chronic - drug therapy Hepatitis C, Chronic - immunology Humans In Vitro Techniques interferon-alpha Interferon-alpha - administration & dosage lymphocyte activation Lymphocyte Activation - drug effects Male Middle Aged Prospective Studies Recombinant Proteins ribavirin Ribavirin - administration & dosage T lymphocytes Th1 Cells - drug effects Th1 Cells - immunology Th2 Cells - drug effects Th2 Cells - immunology Viremia - drug therapy Viremia - immunology |
| title | Effects of interferon and ribavirin combination therapy on CD4+ proliferation, lymphocyte activation, and Th1 and Th2 cytokine profiles in chronic hepatitis C |
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