interleukin-8 and Hepatitis-C--Chronic

Fibromyalgia and chronic hepatitis C infection share many clinical features including prominent somatic complaints such as musculoskeletal pain and fatigue. There is a growing body of evidence supporting a link between cytokines and somatic complaints. This review discusses alterations of cytokines in fibromyalgia, including increased serum levels of interleukin (IL)-2, IL-2 receptor, IL-8, IL-1 receptor antagonist; increased IL-1 and IL-6 produced by stimulated peripheral blood mononuclear cell in patients with FM for longer than 2 years; increased gp130, which is a neutrophil cytokine transducing protein; increased soluble IL-6 receptor and soluble IL-1 receptor antagonist only in patients with fibromyalgia who are depressed; and IL-1 beta, IL-6, and TNF-a by reverse transcriptase-polymerase chain reaction in skin biopsies of some patients with fibromyalgia. In addition, this review describes the mechanism by which alterations in cytokines in fibromyalgia and chronic hepatitis C infection can produce hyperalgesia and other neurally mediated symptoms through the presence of cytokine receptors on glial cells and opiate receptors on lymphocytes and the influence of cytokines on the hypothalamus-pituitary-adrenal axis such as IL-1, IL-6, and TNF-a activating and IL-2 and IFN-a down-regulating the HPA axis, respectively. The association between chronic hepatitis C infection and fibromyalgia is discussed, including a description of key cytokine changes in chronic hepatitis C infection. Future studies are encouraged to further characterize these immunologic alterations with potential pathophysiologic and therapeutic implications.

Topics: Antigens, CD; Biopsy; Cytokines; Fibromyalgia; Hepatitis C, Chronic; Humans; Interleukin-1; Interleukin-2; Interleukin-6; Interleukin-8; Reverse Transcriptase Polymerase Chain Reaction; Skin; Tumor Necrosis Factor-alpha

IL-8 serum levels were measured in a group of 44 patients affected with Chronic Active Hepatitis (CAH) HCV+ at the beginning and end of peg-interferon plus ribavirin combined therapy. IL-8 levels were compared with those measured in a group of healthy controls. The patients were treated for 12 months, and then followed up for 6 months after the end of the therapy. IL-8 serum levels were detected by ELISA at the beginning and end of the therapy, and then at the end of the follow-up. IL-8 serum levels were significantly more elevated (p<0.01) in CAH HCV+ patients than in the healthy controls. Furthermore, IL-8 serum levels in those patients who subsequently showed a sustained virological response to the therapy, declined on treatment and maintained lower levels than in those who did not respond to therapy. Serum IL-8 can be considered and proposed as a non-invasive and predictive marker of response to combined PEG IFN alpha2b + Ribavirin in CAH HCV +.

Topics: Adult; Antiviral Agents; Biomarkers; Data Interpretation, Statistical; Drug Resistance; Drug Therapy, Combination; Enzyme-Linked Immunosorbent Assay; Female; Follow-Up Studies; Genotype; Hepacivirus; Hepatitis C, Chronic; Humans; Interferon alpha-2; Interferon-alpha; Interleukin-8; Male; Polyethylene Glycols; Recombinant Proteins; Ribavirin; RNA, Viral; Time Factors; Treatment Outcome

Efficacy of interferon-alpha2b (IFN) + ribavirin (IFN/RBV) combination in patients with high plasma hepatitis C virus (HCV) is very poor. Dysregulated CD4+ /CD8+ T cells is involved in both impaired cell-mediated immunity and resistance to IFN. Adsorptive granulocytes and monocytes apheresis (GMA) can remove infected leucocytes which are extrahepatic HCV reservoirs and also has been associated with intriguing immunomodulation and increases in CD4+ T cells. Our aim was to see if GMA enhances the efficacy of IFN/RBV. Twenty-four patients, 13 IFN resistant and 11 IFN naive were enrolled. Seventeen were genotype 1b and 7 were 2a or 2b. Mean plasma HCV-RNA was 612.9 (100-850) kIU/mL and alanine aminotransferase, 108 (41-373) U/L. GMA was performed with Adacolumn at one session/day for five consecutive days and IFN/RBV was started within 24 h after the last GMA session. Daily 6 million units of IFN, six times/week for 2 weeks and then three times/week for 22 weeks were given with RBV (600-800 mg/day/patient). Patients were followed for 6 months. GMA was associated with a significant increase in lymphocyte counts, complement activation fragment C3a and falls in tissue necrosis factor-alpha, and IL-8 produced by peripheral blood leucocytes. At week 24, 20 of 24 patients (83%) were HCV negative and by end of follow-up (week 49), the remission was sustained in 14 of 24 patients (58%) including 100% of patients with 2a or 2b. In conclusion, enhanced efficacy of IFN/RBV following GMA might be attributed to a more efficient immune function and a renewed IFN signaling towards HCV.

Topics: Adjuvants, Immunologic; Biopsy, Needle; Combined Modality Therapy; Female; Follow-Up Studies; Hepatitis C, Chronic; Humans; Immunohistochemistry; Interferon alpha-2; Interferon-alpha; Interleukin-8; Leukapheresis; Male; Probability; Prospective Studies; Recombinant Proteins; Ribavirin; Risk Assessment; RNA, Viral; Severity of Illness Index; Statistics, Nonparametric; Treatment Outcome; Tumor Necrosis Factor-alpha; Viral Load

We have shown that treatment with interleukin-2 (IL-2) or interferon-alpha (IFN alpha) may induce depressive symptoms and activation of the cytokine network and that IL-2 treatment may diminish serum dipeptidyl pepdidase IV (DPP IV) activity. DPP IV (EC 3.4.14.5) is a membrane bound serine protease which catalyzes the cleavage of some cytokines and neuroactive peptides which modulate T cell activity. The aims of the present study were to examine the effects of IFN alpha-based immunotherapy on serum DPP IV activity in relation to induction of the inflammatory response system. In 18 patients with chronic active hepatitis C, we determined the Montgomery and Asberg Rating Scale (MADRS), the Hamilton Anxiety Rating Scale (HAM-A), serum DPP IV activity, the kynurenine/tryptophan (K/T) quotient, which is an indicator of cytokine (in particular IFN)-induced catabolism of tryptophan, and serum interleukin-8 (IL-8) before starting therapy and 2, 4, 16 and 24 weeks after immunotherapy with IFN alpha. IFN alpha-immunotherapy significantly suppressed serum DPP IV 2--4 weeks and 16--24 weeks after starting IFN alpha-based immunotherapy. The reduction in serum DPP IV activity was more pronounced 16--24 weeks after starting immunotherapy than after 2--4 weeks. The IFN alpha-induced suppression of serum DPP IV activity was significantly correlated to IFN alpha-induced increases in the MADRS and HAM-A and increases in the K/T quotient and serum IL-8. In conclusion, long-term immunotherapy with IFN alpha suppresses serum DPP IV activity and the immunotherapy-induced changes in DPP IV are related to increases in severity of depression, anxiety and activation of the inflammatory response system.

Topics: Adult; Analysis of Variance; Antiviral Agents; Anxiety Disorders; Biomarkers; Depression; Dipeptidyl Peptidase 4; Dose-Response Relationship, Drug; Female; Hepatitis C, Chronic; Humans; Inflammation; Interferon alpha-2; Interferon-alpha; Interleukin-8; Male; Psychiatric Status Rating Scales; Recombinant Proteins; Regression Analysis; Time Factors

Hepatitis C viral (HCV) infection is a major clinical burden globally. Pegylated IFN-α-2a (PEG-IFN-α-2a) with ribavirin (RIB) therapy induces an array of cellular antiviral responses, including dsRNA kinases (PKR), chemokines, and cytokines to tackle the HCV infection. However, many HCV patients develop resistance to PEG-IFN/RIB therapy rendering the therapy ineffective.. Here, we assess the significance of chemokines in response to PEG-IFN-α-2a with ribavirin (PEG-IFN/RIB) therapy.. Twenty patients with HCV infection and ten healthy controls were enrolled in this study and patients were categorized into two groups 1), HCV-Responder (HCV-R), and 2) HCV-non-responder (HCV-NR). We analyzed IP-10, MIG, MCP-1, EOTAXIN, RANTES, IL-8, MIP-1a, and MIP-1b by a magnetic bead-based multiplex immunoassay approach based on Luminex X-MAP multiplex technology, using a MAGPIX instrument (Luminex Corporation, USA).. A significant elevation of ALT and AST enzymes was observed in HCV-NR. Besides, the PEG-IFN/RIB therapy in both MIG and MCP-1 in HCV-NR patients was significantly induced. PEGIFN/ RIB therapy significantly increased the levels of chemokines, such as IL-8, IP-10, EOTAXIN, MIG, RANTES, and MIP-1β, in HCV-R, indicating the chemokine response to PEG-IFN/RIB therapy.. Hence, MCP-1 and MIG could be the potential biomarkers in HCV-NR and might be associated with the development of liver fibrosis, liver failure, and hepatocellular carcinoma.. Our study has only twenty samples of PEG-IFN/RIB treated HCV patients. This might be the reason for the lack of association between some of the inflammatory markers evaluated and the SVR, therefore, the association found between the chemokine levels observed in the plasma of HCV-R and HCV-NR and EVR cannot be extrapolated to patients infected with other HCV genotypes.

Topics: Antiviral Agents; Biomarkers; Chemokine CCL5; Chemokine CXCL10; Drug Therapy, Combination; Genotype; Hepatitis C, Chronic; Humans; Interferon alpha-2; Interleukin-8; Polyethylene Glycols; Prognosis; Recombinant Proteins; Ribavirin; Treatment Outcome

In this study, strategies for serum biomarker assessment were developed for therapeutic monitoring of HCV patients. For this purpose, serum chemokine/cytokine levels were measured by cytometric-bead-array in HCV patients, categorized according to immunotherapy response as: non-responder/NR, relapser/REL and sustained-virologic-responder/SVR. The results demonstrated an overall increase of serum chemokine/cytokine levels in HCV patients. In general, therapeutic failure was associated with presence of a predominant baseline proinflammatory pattern with enhanced CCL5/RANTES, IFN-α, IFN-γ along with decreased IL-10 levels in NR and increased IL-6 and TNF in REL. SVR displayed lower baseline proinflammatory status with decreased CXCL8/IL-8, IL-12 and IL-17 levels. The inability to uphold IFN-α levels during immunotherapy was characteristic of NR. Serum chemokine/cytokine signatures further support the deleterious effect of proinflammatory baseline status and the critical role of increased/persistent IFN-α levels to guarantee the sustained virologic response. The prominent baseline proinflammatory milieu observed in NR and REL yielded a restricted biomarker network with small number of neighborhood connections, whereas SVR displayed a network with integrated cytokine connectivity. Noteworthy was that SVR presented a shift towards a proinflammatory pattern upon immunotherapy, assuming a pattern similar to that observed in NR and REL at baseline. Moreover, the immunotherapy guided REL towards a profile similar to SVR at baseline. Analysis of baseline-fold changes during treatment pointed out IFN-α and TNF as high-performance biomarkers to monitor immunotherapy outcome. This knowledge may contribute for novel insights into the treatment and control of the continuous public health threat posed by HCV infection worldwide.

Topics: Adult; Aged; Antiviral Agents; Biomarkers, Pharmacological; Chemokines; Cytokines; Drug Monitoring; Female; Hepatitis C, Chronic; Humans; Immunotherapy; Interferon alpha-2; Interferon-alpha; Interleukin-12; Interleukin-17; Interleukin-8; Male; Middle Aged; Polyethylene Glycols; Recombinant Proteins; Viral Load; Young Adult

Schistosome infections are renowned for their ability to induce regulatory networks such as regulatory T cells (Treg) that control immune responses against homologous and heterologous antigens such as allergies. However, in the case of co-infections with hepatitis C virus (HCV), schistosomes accentuate disease progression and we hypothesized that expanding schistosome-induced Treg populations change their phenotype and could thereby suppress beneficial anti-HCV responses. We therefore analysed effector T cells and n/iTreg subsets applying the markers Granzyme B (GrzB) and Helios in Egyptian cohorts of HCV mono-infected (HCV), schistosome-co-infected (Sm/HCV) and infection-free individuals. Interestingly, viral load and liver transaminases were significantly elevated in Sm/HCV individuals when compared to HCV patients. Moreover, overall Treg frequencies and Helios(pos) Treg were not elevated in Sm/HCV individuals, but frequencies of GrzB(+) Treg were significantly increased. Simultaneously, GrzB(+) CD8(+) T cells were not suppressed in co-infected individuals. This study demonstrates that in Sm/HCV co-infected cohorts, liver disease is aggravated with enhanced virus replication and Treg do not expand but rather change their phenotype with GrzB possibly being a more reliable marker than Helios for iTreg. Therefore, curing concurrent schistosome disease could be an important prerequisite for successful HCV treatment as co-infected individuals respond poorly to interferon therapy.

Topics: Adult; Animals; Coinfection; Female; Hepacivirus; Hepatitis C, Chronic; Humans; Interleukin-8; Liver; Male; Middle Aged; Schistosoma mansoni; Schistosomiasis mansoni; T-Lymphocytes, Regulatory; Viral Load

Topics: Female; Hepatitis C, Chronic; Humans; Interleukin-8; Male; T-Lymphocytes, Regulatory

Topics: Female; Hepatitis C, Chronic; Humans; Interleukin-8; Male; T-Lymphocytes, Regulatory

The aim of this study was to assess whether physical performance correlates with metabolic and inflammatory measures in research subjects with chronic liver disease.. This is a prospective, descriptive cohort study correlating performance on a 6-min walk test with cardiorespiratory variables, metabolic measures (glucose [GLU], C-peptide insulin, and lipids), liver enzymes (aspartate aminotransferase and alanine aminotransferase), and the proinflammatory cytokine interleukin-8 (IL-8).. This study enrolled 51 subjects (18 women) with chronic liver disease: 41% (n = 21) with nonalcoholic fatty liver disease and 59% (n = 30) with hepatitis C virus. Age, resting heart rate, and fasting GLU correlated significantly with distance walked (P's < 0.05). First quartile "poor performers" (n = 14) and fourth quartile "high performers" (n = 14) showed differences in age, sex, fasting GLU, and IL-8 level (P's < 0.05). Combining the number of abnormal serum values (IL-8, C-peptide insulin, GLU, aspartate aminotransferase, alanine aminotransferase, high-density lipoprotein, triglyceride, and total cholesterol) did not correlate with distance walked (P > 0.90). However, in multiple regression analysis, a model that included sex, age, resting heart rate, IL-8 level, and fasting GLU level explained approximately 39% of the variance in the distance walked during the test.. Older age, female sex, abnormal levels of the proinflammatory cytokine IL-8, abnormalities of GLU metabolism, and high resting heart rate are associated with poor physical performance in subjects with chronic liver disease. Poor physical performance is associated with physiologic, metabolic, and inflammatory abnormalities in subjects with nonalcoholic fatty liver disease and hepatitis C virus.

Topics: Age Factors; Blood Glucose; Exercise Test; Fatty Liver; Female; Heart Rate; Hepatitis C, Chronic; Humans; Interleukin-8; Male; Middle Aged; Physical Fitness; Prospective Studies; Regression Analysis; Rest; Sex Factors; Walking

The host immune response is closely related to the prognosis of disease and viral persistence in hepatitis B (HBV) and hepatitis C virus (HCV) infections. Although it is well known that cytokines and genetic factors play important roles in the pathogenesis of chronic HBV and HCV infections, the underlying mechanisms are not fully understood. This study was conducted to determine the role of interleukin (IL)-1β, IL-1 receptor antagonist (IL-1RA) and IL-8 gene polymorphisms in chronic hepatitis B and C infections. A total of 361 subjects, 171 with chronic hepatitis B (62 female, 109 male; age range: 18-74 yrs) and 104 with chronic hepatitis C (63 female, 41 male; age range: 25-79 yrs), and a control group of 86 healthy subjects (41 female, 45 male; age range: 18-72 yrs) were included in the study. Following the DNA extractions from peripheral blood leukocytes of the study groups, single nucleotide polymorphisms of IL-1β -31, -511, +3954; IL-1RA and IL-8 -251, -353, -738, -845 gene regions were investigated by using specific primers with real-time PCR method. It was found that the genotype frequency of IL-8 -251 AT (OR: 7.895, p= 0.003) and IL-8 -738 TA (OR: 6.317, p= 0.007) in patients with chronic hepatitis B and the genotype frequency of IL-1β-31 CT (OR: 6.757, p= 0.001), IL-1β -511 CT (OR: 4.060, p= 0.004), IL-8 -251 AT, (OR: 13.622, p= 0.001), IL-8 -738 TA (OR: 14.058, p= 0.001), and IL-8 -845 TC (OR: 2.539, p= 0.004) in patients with chronic hepatitis C was significantly higher than the control group. When the allelic frequency was compared between chronic hepatitis B patients and the control group, it was determined that IL-1β +3954 T allel increased the disease risk 1.5 times (p< 0.05), however, no statistically significant difference was detected for the other allels. It was also determined that IL-8 -845 C allel increased the disease risk 0.6 times in chronic hepatitis C (p< 0.05) and no statistically significant difference was detected for the other allels (p> 0.05). In conclusion, IL-1β -31, -511 and IL-8 -251, -738, -845 gene polymorphisms may play a role in the chronicity of hepatitis B and C infection. In order to determine the importance of this cytokine polymorphisms in hepatitis B and hepatitis C virus infections, large-scale studies with different patient groups such as carriers, chronic hepatitis, cirrhosis, and hepatocellular carcinoma should be conducted to elucidate the molecular mechanisms underlying the disease process.

Topics: Adolescent; Adult; Aged; Case-Control Studies; DNA; Female; Gene Frequency; Hepatitis B, Chronic; Hepatitis C, Chronic; Humans; Interleukin-1beta; Interleukin-8; Male; Middle Aged; Polymorphism, Genetic; Receptors, Interleukin-1; Risk Factors; Young Adult

Low-level hepatitis C virus (HCV) RNA may persist in PBMCs after successful treatment of chronic hepatitis C, but the consequences of this phenomenon are unclear. Forty-nine patients who achieved a sustained virological response (SVR) after pegylated IFN and ribavirin therapy were analysed 52-66 months after the SVR. HCV RNA was detected in PBMCs from 18 patients (47.4 %), and PBMCs in two patients stained positive for non-structural protein 3 (NS3). Quantification of various cytokine and chemokine transcripts in PBMCs revealed that levels of IL-6, IL-8, IL-12, TNF-α and macrophage inflammatory protein 1β were significantly higher in HCV-positive patients than in HCV-negative individuals. In conclusion, persistence of HCV RNA in PBMCs of patients with a SVR appears to be associated with immune activation.

Topics: Alanine Transaminase; Antiviral Agents; Chemokine CCL4; Drug Therapy, Combination; Female; Hepacivirus; Hepatitis C, Chronic; Humans; Interferon-alpha; Interleukin-12 Subunit p35; Interleukin-6; Interleukin-8; Leukocytes, Mononuclear; Male; Middle Aged; Polyethylene Glycols; Recombinant Proteins; Ribavirin; RNA, Viral; Treatment Outcome; Tumor Necrosis Factor-alpha; Viral Load; Viral Nonstructural Proteins

Regulatory CD4(+) T cells (Tregs) are considered to affect outcomes of HCV infection, because they increase in number during chronic hepatitis C and can suppress T-cell functions.. Using microarray analysis, in situ immunofluorescence, ELISA, and flowcytometry, we characterised functional differentiation and localisation of adaptive Tregs in patients with chronic hepatitis C.. We found substantial upregulation of IL-8 in Foxp3(+)CD4(+) Tregs from chronic hepatitis C. Activated GARP-positive IL-8(+) Tregs were particularly enriched in livers of patients with chronic hepatitis C in close proximity to areas of fibrosis and their numbers were correlated with the stage of fibrosis. Moreover, Tregs induced upregulation of profibrogenic markers TIMP1, MMP2, TGF-beta1, alpha-SMA, collagen, and CCL2 in primary human hepatic stellate cells (HSC). HSC activation, but not Treg suppressor function, was blocked by adding a neutralizing IL-8 antibody.. Our studies identified Foxp3(+)CD4(+) Tregs as an additional intrahepatic source of IL-8 in chronic hepatitis C acting on HSC. Thus, Foxp3(+)CD4(+) Tregs in chronic hepatitis C have acquired differentiation as regulators of fibrogenesis in addition to suppressing local immune responses.

Topics: Adaptive Immunity; Adult; Aged; Biomarkers; Disease Progression; Female; Fibrosis; Forkhead Transcription Factors; Hepatic Stellate Cells; Hepatitis C, Chronic; Humans; Interleukin-8; Liver; Male; Middle Aged; T-Lymphocytes, Regulatory; Up-Regulation; Young Adult

Chronic hepatitis C virus (HCV) infection is a major risk factor for hepatocellular carcinoma (HCC). HCV proteins core and NS3 can bind to toll-like receptor 2 (TLR2) and trigger inflammatory responses. Polymorphisms in the TLR2 gene predispose to various forms of malignancy but have not been studied in HCV-associated HCC. Here, we investigated whether single nucleotide polymorphisms (SNPs), rs4696480, rs5743708, rs5743704 and the -196 to -174 del/ins polymorphism of the TLR2 gene affect the risk for HCC in chronic hepatitis C. The study involved 189 and 192 HCV genotype 1 infected patients with and without HCC, respectively, as well as 347 healthy controls. TLR2 alleles were determined by hybridization probe assays and allele-specific short fragment polymerase chain reaction on a LightCycler system. All TLR2 polymorphisms matched the Hardy-Weinberg equilibrium in each study group. Although TLR2 SNPs showed no effect, the frequency of the TLR2 -196 to -174 del allele was significantly higher in patients with HCV-associated HCC (22.5%) than in HCV-infected patients without HCC (15.6%, p = 0.016) and healthy controls (15.3%, p = 0.003). HCV-infected carriers of a TLR2 -196 to -174 del allele had significantly higher HCV viral loads than TLR2 -196 to -174 ins/ins homozygous patients (p = 0.031). Finally, in carriers of the TLR2 -196 to -174 del allele, stimulation of monocytes resulted in significantly lower TLR2 expression levels and interleukin-8 (IL-8) induction than in individuals with the TLR2 -196 to -174 ins/ins genotype (p < 0.05). Our data suggest the TLR2 -196 to -174 del allele to affect HCV viral loads and to increase the risk for HCC in HCV genotype1-infected patients.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Alleles; Carcinoma, Hepatocellular; Case-Control Studies; Female; Genetic Predisposition to Disease; Genotype; Hepacivirus; Hepatitis C, Chronic; Humans; Interleukin-8; Liver Neoplasms; Male; Middle Aged; Polymorphism, Genetic; Toll-Like Receptor 2; Viral Load; Young Adult

The Th17-mediated immune response was investigated in patients chronically infected with hepatitis C virus (HCV) by determining the serum levels of the cytokines involved in the induction of the Th17 response (TGF-β and IL-6), the cytokines produced by Th17 cells (IL-17A, IL-17F and IL-22) and the cytokines whose production is stimulated by Th17 lymphocytes (IL-8 and GM-CSF). We investigated the relationships among the levels of these cytokines by assessing clinical findings, liver histology and viremia. Sixty untreated patients and 28 healthy individuals were included in the study. Cytokine levels were determined using ELISA. Differences between HCV and control groups were identified in the median levels of IL-17F (controls=172.4 pg/mL; HCV=96.8 pg/mL, p<0.001) and IL-8 (controls=30.1 pg/mL; HCV=18.1 pg/mL, p<0.05). IL-6 levels were higher in patients presenting moderate liver necroinflammation than in patients with mild or no liver necroinflammation (p<0.05). IL-17F levels were increased in patients that had increased ALT levels. Additionally, a strong positive correlation was observed between IL-17F and IL-22 levels in the two groups investigated, and the IL-17F/IL-22 ratio was lower in the patients infected with HCV (p<0.0001). Patients with low HCV viral loads had higher median levels of IL-8 (32.5 pg/mL) than did patients with high HCV loads (16.7 pg/mL, p<0.05). These results suggest that in chronic hepatitis C infection, IL-17F and IL-8 could be associated with the control of liver injury and infection, respectively.

Topics: Adult; Aged; Alanine Transaminase; Cytokines; Enzyme-Linked Immunosorbent Assay; Female; Granulocyte-Macrophage Colony-Stimulating Factor; Hepacivirus; Hepatitis C, Chronic; Host-Pathogen Interactions; Humans; Interleukin-17; Interleukin-22; Interleukin-6; Interleukin-8; Interleukins; Liver; Male; Middle Aged; Th17 Cells; Transforming Growth Factor beta; Viral Load

Hepatitis C virus (HCV), a major cause of liver disease throughout the world, is difficult to treat with interferon (IFN) (and various formulations and combinations thereof) being the only approved molecule available. It has been investigated recently that proinflammatory chemokine interleukin-8 (IL-8) induced by HCV partially inhibits the antiviral IFN-α therapy. Therefore, the current study was aimed to prospectively utilize the baseline IL-8 levels in the HCV infected serum and predicts its role in sustained virological response (SVR) to IFN-α+ribavirin therapy, in chronic HCV patients in Pakistan. One hundred and ten hepatitis C patients without any other infections underwent IFN-α+ribavirin combination treatment. Baseline IL-8 levels were determined before starting of the therapy for all these patients. Fifteen normal volunteers negative for HCV were kept as control. The baseline IL-8 levels were found significantly higher in all HCV positive patients as compared to normal healthy volunteers (1083.54 ± 85.72 pg/ml versus 6.99 ± 1.05 pg/ml [mean ± SEM], p<0.01) and were also significantly higher in non-responders than responders (p<0.05). Comparatively higher mean baseline IL-8 levels were observed in non-responders (2442.02 ± 159.92 pg/ml), than late (1009.31 ± 45.31) and rapid (540.91 ± 27.06 pg/ml) responders. Significant relation was observed between baseline IL-8 level and response to IFN therapy (p<0.01). Results of this study suggest that increased levels of IL-8 in HCV infection might be involved in pathogenesis, persistence and resistance to IFN-α+ribavirin combination therapy.

Topics: Adolescent; Adult; Aged; Analysis of Variance; Case-Control Studies; Drug Therapy, Combination; Female; Genotype; Hepacivirus; Hepatitis C, Chronic; Humans; Interferon Type I; Interleukin-8; Male; Middle Aged; Pakistan; Reference Values; Ribavirin; Risk Factors; Treatment Failure; Viral Load; Young Adult

Hepatitis C virus (HCV)-associated antigens, such as the core and nonstructural antigens, activate host innate immune systems via Toll-like receptors (TLRs). We previously showed that chronic exposure to the core antigen induces hyporesponsiveness to TLR ligands in antigen-presenting cells via activation of TLR2 and that stimulation with TLR ligands results in impaired IL-6 production by peripheral blood monocytes from HCV-infected patients. In the present study, peripheral blood mononuclear cells (PBMCs) isolated from patients with chronic HCV or hepatitis B virus (HBV) infection were stimulated with TLR ligands to determine the production of IL-6 and IL-8 and to identify the clinical parameters associated with hyporesponsiveness to TLR ligands in patients with chronic HCV infection. The results showed that pro-inflammatory cytokine responses to TLR ligands were suppressed in PBMCs isolated from HCV-infected, but not HBV-infected, patients. The reduced cytokine responses to TLR ligands seen in HCV-infected patients correlated with platelet counts and serum prothrombin time levels. In contrast, there was no correlation between TLR-induced cytokine responses and serum levels of core antigen. Thus, hyporesponsiveness to TLR ligands in HCV-infected patients is correlated with liver dysfunction. In conclusion, both host factors and viral factors may be involved in the generation of hyporesponsiveness to TLR ligands in patients with chronic HCV infection.

Topics: Adult; Aged; Antigens, Viral; Female; Hepacivirus; Hepatitis B; Hepatitis C, Chronic; Humans; Interleukin-6; Interleukin-8; Leukocytes, Mononuclear; Liver Diseases; Male; Middle Aged; Platelet Count; Prothrombin Time; Toll-Like Receptors

Hepatitis C virus (HCV) core and nonstructural (NS) 3 proteins induce inflammation and immunity through a toll-like receptor (TLR) 2-dependent pathway. Individuals with the R753Q single-nucleotide polymorphism (SNP) in the TLR2 gene have increased the risk of allograft failure after liver transplantation for chronic hepatitis C.. To test the hypothesis that R753Q SNP impairs TLR2 recognition of HCV proteins, a series of in vitro experiments were performed wherein stable clones of wild-type TLR2-deficient human embryonic kidney (HEK) 293 cells and HEK293 cells transfected with wild-type (HEK293-TLR2) or variant TLR2 genes (HEK293-TLR2-R753Q) were stimulated with HCV core and NS3 proteins. Cellular activation was assessed by nuclear factor-kappa B-driven luciferase activity, cytokine secretion, and gene upregulation.. Compared with TLR2-deficient HEK293 cells, HEK293-TLR2 cells had marked nuclear factor-kappa B-driven luciferase activity, had modest to marked upregulation in TLR2 signaling-associated genes, and secreted large quantities of interleukin-8 during exposure to HCV core and NS3 proteins. In contrast, HEK293-TLR2-R753Q cells did not respond to stimulation with HCV and behaved similarly like TLR2-deficient HEK293 cells.. R753Q SNP impairs TLR2-mediated immune recognition of HCV core and NS3 proteins. This biologic defect may account for the predisposition of patients to develop allograft failure after liver transplantation for chronic hepatitis C.

Topics: Cell Line; Gene Expression Regulation; Genes, Reporter; Graft Survival; Hepatitis C, Chronic; Humans; Immunity, Innate; Interleukin-8; Liver Transplantation; NF-kappa B; Polymorphism, Single Nucleotide; Promoter Regions, Genetic; Toll-Like Receptor 2; Transfection; Transplantation, Homologous; Viral Core Proteins; Viral Nonstructural Proteins

LIGHT (TNFSF 14) belongs to the tumor necrosis factor superfamily and is expressed by activated T cells as well as various types of antigen presenting cells. LIGHT binds to its cellular receptors TR2 and LTbetaR and has a co-stimulatory role in T cell activation. Here, we compared the relative expression of LIGHT in different immune cells and the biological activity of immune cell-derived LIGHT on endothelial cells.. Surface expression of LIGHT and mRNA production by PBMC and isolated T cells (CD4+ or CD8+) significantly increased after stimulation with PMA (Phorbolester-12- Myristat-13-Acetat)+ionomycin. No LIGHT expression on PMA stimulated monocytes or monocytic-like THP-1 cells could be detected; differentiation of monocytes and THP-1 cells into macrophages, however, resulted in up-regulation of LIGHT. Supernatants of stimulated T cells contained higher concentrations of soluble LIGHT than macrophage supernatants normalized to cell numbers; release of soluble LIGHT was found to be dependent on metalloproteinase activity. Size determination of released soluble LIGHT by size exclusion chromatography revealed a molecular mass of approximately 60 kDa, suggesting a trimeric form. Released soluble LIGHT induced expression of proinflammatory antigens ICAM-1, tissue factor and IL-8 in human endothelial cells and caused apoptosis of IFN-g pretreated endothelial cells. Soluble LIGHT was detected at low levels in sera of healthy controls and was significantly enhanced in sera of patients with chronic hepatitis C and rheumatoid arthritis (24.93+/-9.41 vs. 129.53+/-49.14 and 172.13+/-77.64; p<0.0005).. These findings suggest that among immune cells activated T lymphocytes are the main source of soluble LIGHT with released amounts of soluble LIGHT markedly higher compared to platelets. Immune cell-derived membrane-bound and soluble trimeric LIGHT is biologically active, inducing proinflammatory changes in endothelial cells. Enhanced plasma levels of soluble LIGHT in patients with chronic infections suggest a role of LIGHT in systemic inflammatory activation.

Topics: Adolescent; Adult; Aged; Arthritis, Rheumatoid; Cell Differentiation; Cells, Cultured; Drug Combinations; Endothelium, Vascular; Enzyme-Linked Immunosorbent Assay; Female; Gene Expression; Hepatitis C, Chronic; Humans; Intercellular Adhesion Molecule-1; Interleukin-8; Ionomycin; Leukocytes, Mononuclear; Macrophages; Middle Aged; Molecular Weight; RNA, Messenger; T-Lymphocytes; Tetradecanoylphorbol Acetate; Thromboplastin; Tumor Necrosis Factor Ligand Superfamily Member 14; Umbilical Veins; Up-Regulation; Young Adult

Gene expression technologies allow the analysis of gene networks whose expression is associated with specific pathological conditions compared with normal tissue. We hypothesized that histologically normal tissue obtained in different ways (percutaneous or surgical liver biopsies), usually used as normal controls in gene expression studies, could have different gene expression patterns. Group A comprised percutaneous liver biopsies in 14 patients with mildly elevated alanine aminotransferase in whom all causes of liver disease had been ruled out. Group B comprised 14 surgical liver biopsies of nontumoral livers. All 28 specimens were histologically normal. Real-time quantitative reverse-transcription polymerase chain reaction were used to compare the messenger RNA expression of 240 selected genes in these two groups. Expression of 26 of the 240 genes was significantly different between groups A and B; 23 genes were up-regulated in group A, while three were down-regulated in group B. The most notable changes occurred in the inflammatory response family genes. Eight genes discriminated perfectly between groups A and B: seven up-regulated genes (PAI1, THBS1, IL8, PTGS2, CXCR4, JUN, and FOS), and one down-regulated gene (IHH). In chronic hepatitis C liver samples, a lower or higher expression of a IL8 was found depending on whether the controls were obtained percutaneously or surgically.. Our study demonstrates that histologically normal liver tissue obtained in two different ways (percutaneous or surgical) has different gene expression patterns emphasizing the importance of an adequate selection of histologically normal controls to prevent discordant results in gene expression studies.

Topics: Biopsy; Cyclooxygenase 2; Gene Expression Profiling; Hepatitis C, Chronic; Humans; Interleukin-18; Interleukin-8; Liver; Plasminogen Activator Inhibitor 1; Proto-Oncogene Proteins c-fos; Proto-Oncogene Proteins c-jun; Receptors, CXCR4; Reproducibility of Results; RNA, Messenger; Thrombospondin 1

PREMISES AND OBJECTIVES: The evolution of the infection with the hepatic virus C depends on the defense of the organism, found under the control of a network of cytokines and chemokines. The mechanisms that are causing both viral persistence as well as hepatic pathology are not entirely elucidated. We have proposed to study the amount in which different categories of cytokines are incriminated in the pathogenesis of the chronic liver disease, as well as the eventual correlations between the serum levels of these cytokines and certain histopathological aspects in the chronic viral hepatitis C.. Thirty-five patients with chronic viral hepatitis C (persistent - nine, active - 15, cirrhosis - 11) have been studied, constituting group P, and 20 healthy subjects constituting the reference group (R). In both groups have been determined the serum concentrations of some proinflammatory interleukins (TNF-alpha, IL-6, IL-8), and antiinflammatory (IL-10) cytokines, through the immunoenzymatic technique ELISA. Results. For the proinflammatory cytokines taken into consideration (TNF-alpha, IL-6, IL-8) increased serum values have been determined to the patients with chronic hepatitis C, the maximal level being observed to the patients active chronic hepatitis and cirrhosis (24/35 patients - 68.57%, 19/35 patients - 54.28% and, namely, 18/35 patients - 51.42%). The serum values of IL-10 are increased in 19/35 patients - 54.28%. The direct relationship among the increased levels of IL-10, the astringency of the inflammation and the hepatic functional insufficiency has been taken into consideration.. The immune cellular answer has a fundamental role in the pathogenesis of the liver disease in the patients with chronic viral hepatitis C. The disequilibrium between the pro- and antiinflammatory cytokines participates to the installation of hepatic lesions of cytolysis and/or to the progression of fibrosis. The serum concentrations of the studied cytokines (TNF-alpha, IL-6, IL-8 and IL-10) are correlated to the histopathological spoilages of the liver.

Topics: Biopsy; Case-Control Studies; Cytokines; Hepatitis C, Chronic; Humans; Inflammation Mediators; Interleukin-6; Interleukin-8; Interleukins; Liver Cirrhosis; Tumor Necrosis Factor-alpha

The current study was designed to investigate the contribution of chemokines to the pathogenesis of chronic hepatitis C and hepatocellular carcinoma (HCC) by measuring the production of IL-8, monocyte chemoattractant protein-1 (MCP-1) and macrophage inflammatory protein-1 alpha (MIP-1alpha). A solid-phase sandwich enzyme-linked immunosorbent assay (ELISA) was established to quantitate serum concentrations of the chemokines. Expression of chemokines in liver tissues was evaluated immunohistochemically using specific monoclonal antibodies. As the severity of chronic hepatitis escalated, serum IL-8 levels increased progressively. Moreover, in the hepatocellular carcinoma (HCC) patients, IL-8 concentrations were positively correlated with the macroscopic staging of HCC, and inversely correlated with the duration of the survival periods. The results demonstrate that IL-8 production may be augmented upon the malignant transformation of hepatocytes in chronic hepatitis C.

Topics: Adult; Aged; Carcinoma, Hepatocellular; Chemokine CCL2; Chemokine CCL3; Chemokines, CC; Disease Progression; Enzyme-Linked Immunosorbent Assay; Female; Hepatitis C, Chronic; Humans; Immunohistochemistry; Interleukin-8; Liver; Liver Neoplasms; Male; Middle Aged; Neoplasm Staging; Survival Analysis

Chronic hepatitis C virus (HCV) infection is characterized by an insufficient immune response, possibly owing to impaired function of antigen-presenting cells such as myeloid dendritic cells (DCs). Therapeutic vaccination with in vitro generated DCs may enhance the immune response. Subsets of DCs can originate from monocytes, but the presence of HCV in monocytes that develop into DCs in vitro may impair DC function. Therefore, we studied the presence of HCV RNA in monocytes and monocyte-derived DCs from chronic HCV patients.. Monocytes were cultured with granulocyte macrophage colony-stimulating factor (GM-CSF) and interleukin 4 (IL-4) for 6 days, and then with GM-CSF, IL-4, tumour necrosis factor-alpha (TNF-alpha), prostaglandin E2, IL-1beta and IL-6 for 2 days to generate mature DCs. HCV RNA was assessed by polymerase chain reaction. Surface molecules were assessed by flow cytometry. Cytokine production was assessed by cytokine bead array.. HCV RNA was present in monocytes in 11 of 13 patients, but undetectable in mature DCs in 13 of 13 patients. The morphology of patient DCs was comparable with DCs from healthy controls, but the percentage of cells expressing surface molecules CD83 (P=0.001), CD86 (P=0.023) and human leucocyte antigen-DR (P=0.028) was lower in HCV patients. Compared with control DCs, patient DCs produced enhanced levels of IL-10 (P=0.0079) and IL-8 (P=0.0079), and lower levels of TNF-alpha (P=0.032), IL-6 (P=NS) and IL-1beta (P=0.0079). Patient and control DCs did not produce IL-12.. Monocyte-derived DCs from chronic HCV patients are not infected but show an immature phenotype and aberrant cytokine profile.

Topics: Adult; Antigens, CD; B7-2 Antigen; Case-Control Studies; CD83 Antigen; Cells, Cultured; Cytokines; Dendritic Cells; Female; Hepacivirus; Hepatitis C, Chronic; HLA-DR Antigens; Humans; Immunity, Cellular; Immunity, Innate; Immunoglobulins; Interleukin-10; Interleukin-1beta; Interleukin-6; Interleukin-8; Lymphocytes; Male; Membrane Glycoproteins; Middle Aged; Monocytes; Phenotype; RNA, Viral; Time Factors; Tumor Necrosis Factor-alpha

HIV co-infection is associated with reduced HCV treatment response rates and accelerated HCV-related liver disease. Cytokines play an important role in regulating hepatic inflammation and fibrogenesis during chronic HCV infection, yet the roles of HIV and/or its therapies on cytokine expression are unknown. Total RNA was extracted from liver biopsies of 12 HCV mono-infected and 14 HCV/HIV co-infected persons. We used real-time PCR to quantify cytokines that contribute to innate and adaptive immune responses, including IFNalpha, IFNgamma, TNFalpha, TGFbeta(1), IL-2, IL-4, IL-8, IL-10, and IL-12p40. Positive- and negative-strand HCV RNA levels were quantified using a molecular beacon approach. Detection of positive-strand HCV RNA was 100% in both groups; negative-strand HCV RNA was detected in four (33%) HCV mono-infected persons and in nine (64%) HCV/HIV co-infected persons. Median strand-specific HCV RNA levels were not significantly different between the two groups. Detection rates of cytokine mRNAs were lower for the HCV/HIV co-infected group compared to the HCV mono-infected group; the detection rates for TNFalpha, IL-8, and IL-10 were statistically significant. Overall, cytokine mRNA quantities were lower for HCV/HIV co-infected compared to HCV mono-infected persons, with the exception of TGFbeta1. These data suggest that a defect in cytokine activation may occur in HCV/HIV co-infected persons that limits efficient clearance of HCV from the liver.

Topics: Biopsy; Cytokines; Down-Regulation; Female; Hepacivirus; Hepatitis C, Chronic; HIV Infections; Humans; Interleukin-10; Interleukin-8; Liver; Male; Polymerase Chain Reaction; Retrospective Studies; RNA, Viral; Tumor Necrosis Factor-alpha

The cellular and humoral natural immune response induced by hepatitis C virus (HCV) is commonly unable to eradicate the virus. HCV is a highly mutable, hepatotropic RNA virus that causes acute and chronic hepatitis, an infection that involves the production of various cytokines. The aim of the study is to analyse the expression of pro-inflammatory cytokines IL-1beta, TNF-alpha, IFN-gamma and the chemokine CXCL8 (IL-8) in liver tissue and their expression and secretion in PBMC of patients with chronic hepatitis C (CHC), in response to pentoxyfilline (PTX). We studied six CHC patients, naive to treatment. Patients received PTX 400 mg twice a day/8 weeks. Pentoxyfilline resulted in decreased expression of mRNA of liver IL-1beta, TNF-alpha and IFN-gamma: 144.2 versus 83.5 molecules of IL-1beta (P < 0.05), TNF-alpha 194.3 versus 17.6 molecules (P = 0.03) and IFN-gamma 26.1 versus 0.5 molecules (P = 0.04). Following PTX, PBMC exhibited a decrease in IFN-gamma mRNA 12.2 versus 1.5 molecules (P = 0.028) and CXCL8 4.2 versus 2.5 molecules (P = 0.027). In PBMC, only the secretion of TNF-alpha was decreased 1109 versus 933.5 pg/ml, P = 0.046. Production of cytokines both locally (within the liver) and systemically (PBMC) may serve as biomarkers of the infection with hepatitis C. PTX inhibits the expression of several pro-inflammatory cytokines in the liver. These results indicate that it is worth exploring PTX in hepatitis in future clinical trials in nonresponders to antiviral treatment.

Topics: Adult; Cytokines; Female; Hepacivirus; Hepatitis C, Chronic; Humans; Inflammation Mediators; Interferon-gamma; Interleukin-1; Interleukin-8; Middle Aged; Pentoxifylline; RNA, Messenger; Tumor Necrosis Factor-alpha

Upregulation of interleukin-8 by the hepatitis C virus non-structural-5A-protein leads to inhibition of the antiviral activity of interferon-alpha in vitro. The clinical significance of interleukin-8 levels for virologic response to interferon-alpha-based treatment in patients with chronic hepatitis C is unknown.. We investigated serum interleukin-8 in 59 healthy controls and 214 patients with chronic hepatitis C (genotype 1, n=152; genotype 2, 3, n=62) and different outcome to interferon-alpha-based therapy.. In patients with chronic hepatitis C higher interleukin-8 levels were observed compared with healthy controls (P<0.0001). Hepatitis C genotype 1-infected patients with early and overall virologic response to interferon-alpha-based therapy showed lower interleukin-8 levels than non-responders (P=0.025 and P=0.035, respectively). In all patients, elevated interleukin-8 levels were associated with cirrhosis (genotype 1, P=0.0003; genotype 2, 3, P=0.009). Interleukin-8 levels in sustained virologic responders were still higher 24 weeks after the end-of-therapy compared with healthy controls (P<0.0001).. In genotype 1 infected patients, low pretreatment serum interleukin-8 is associated with virologic response to interferon-alpha-based therapy. Thus, the conclusion from in vitro studies that the upregulation of interleukin-8 by the hepatitis C virus contributes to the inhibition of the antiviral actions of interferon-alpha may also be applicable in vivo.

Topics: Adult; Aged; Antiviral Agents; Case-Control Studies; Female; Genotype; Hepacivirus; Hepatitis C, Chronic; Humans; Interferon alpha-2; Interferon-alpha; Interleukin-8; Male; Middle Aged; Polyethylene Glycols; Recombinant Proteins; Viral Nonstructural Proteins

The role of a cyclooxygenase (COX) II inhibitor in reducing microvascular inflammation and the platelet count associated with interferon (IFN) plus ribavirin therapy of chronic hepatitis C (HCV) was assessed. Three plasma mediators (biomarkers) associated with platelet activation, inflammation and fibrosis were measured. Eighteen IFN naïve patients were studied. Nine were treated with pegylated IFN alfa-2a (PEG-IFN alpha-2a) plus ribavirin and rofecoxib; nine were treated with PEG-IFN alpha-2a plus ribavirin. A complete blood count, liver panel and HCV-RNA were assayed weekly. Human soluble P-selectin (hs-P-selectin), human interleukin-8 (IL-8), human interleukin-13 (IL-13) and human thrombopoietin (TPO) were assayed at 4 week intervals. The COX II inhibitor reduced the platelet reduction experienced with PEG-IFN alpha-2a treatment of HCV despite a reduction in the plasma TPO level. Hs-P-selectin was increased in both groups. In contrast, human IL-8 levels declined to undetectable levels in virologic responders. Similarly, human IL-13 levels declined with therapy (P < 0.001). These data suggest that: (1) a COX II inhibition is associated with an increase in the platelet count despite a reduction in the TPO level; (2) human IL-8 and human IL-13 but not hs-P-selectin levels decline in those who experience an early virologic response.

Topics: Antiviral Agents; Biomarkers; Blood Platelets; Cyclooxygenase 2; Cyclooxygenase 2 Inhibitors; Cyclooxygenase Inhibitors; Drug Carriers; Drug Therapy, Combination; Hepacivirus; Hepatitis C, Chronic; Humans; Interferon alpha-2; Interferon-alpha; Interleukin-13; Interleukin-8; Membrane Proteins; Middle Aged; P-Selectin; Polyethylene Glycols; Prostaglandin-Endoperoxide Synthases; Recombinant Proteins; Ribavirin; Viral Load

The success of interferon-alpha and ribavirin combination therapy for the treatment of chronic hepatitis C viral infection differs between patients. In an attempt to identify predictors of host response to therapy, the levels of mRNA for interferon (IFN) stimulated genes: MxA, PKR, 2'5' OAS, ISG15, and interleukin 8 (IL-8), were examined in liver by real-time RT-PCR prior to commencement of therapy. The levels of intrahepatic classical IFN stimulated genes, but not IL-8, in chronic HCV disease (n = 44) were found to be significantly upregulated (P < 0.001) compared to the control cohort (n = 12). The genotype of the infecting HCV strain did not influence IFN stimulated gene expression. These results suggest that the endogenous type 1 IFN antiviral effector pathway is broadly activated during chronic HCV disease, although the levels of mRNA for any of the IFN-stimulated genes tested did not predict the outcome of combination therapy.

Topics: 2',5'-Oligoadenylate Synthetase; Adult; Cytokines; Drug Therapy, Combination; eIF-2 Kinase; Female; GTP-Binding Proteins; Hepacivirus; Hepatitis C, Chronic; Humans; Interferon alpha-2; Interferon-alpha; Interferons; Interleukin-8; Liver; Liver Diseases; Male; Myxovirus Resistance Proteins; Proteins; Recombinant Proteins; Ribavirin; RNA, Messenger; Ubiquitins; Up-Regulation

Recombinant human intercrine reduced in hepatomas (hIRH)/stromal cell-derived factor 1 (SDF1-alpha)/pre-B-cell growth-stimulating factor (PBSF), a new chemokine, exhibits an in vitro chemotaxis to neutrophils and a mixed in vivo chemotactic activity to neutrophils, lymphocytes, and monocytes in a rat intradermal injection model. We have investigated the messenger RNA (mRNA) expression of interleukin-8 (IL-8) and hIRH, in chronic hepatitis C of differing severity. Levels of expression of IL-8 and hIRH mRNA obtained from 37 human liver biopsy samples were measured by reverse-transcription and semiquantitative polymerase chain reaction (RT-PCR) amplification. We examined the correlation between mRNA expression and components of the histological activity index (HAI). Patients with HAI > or = 8 had a significantly higher corrected IL-8 mRNA expression ratio (0.24 +/- 0.13 [mean +/- SD]; n = 20) than those with HAI < or = 7 (0.05 < or = 0.03; n = 17; P < .0001). Additionally, IL-8 mRNA expression was strongly associated with the severity of portal inflammation (PI) (high PI vs. low PI, 0.22 +/- 0.14 vs. 0.05 +/- 0.04; P < .0001) and with the presence of bile duct lesions (0.29 +/- 0.15 vs. 0.11 +/- 0.1; P < .01). In contrast, hIRH mRNA expression was not associated with the total HAI, any components of the HAI, or bile duct inflammation or injury. These results suggest that hIRH, although having the -CXC-, alpha chemokine motif, and exhibiting in vivo and in vitro inflammatory activity as does IL-8, plays a different role from IL-8 in hepatic inflammation and injury. IL-8 expression is directly associated with inflammation in patients with chronic hepatitis C, while hIRH expression does not correlate with histopathological severity of inflammation.

Topics: Animals; Chemokine CXCL12; Chemokines, CXC; Chemotactic Factors; Chemotaxis, Leukocyte; Hepatitis C, Chronic; Hepatitis, Animal; Humans; Interleukin-8; Neutrophils; Rats; Recombinant Proteins; RNA, Messenger

Lymphocyte adhesion to endothelium, extravasation, and adhesion to hepatocytes are mediated by adhesion molecules and constitute important steps in the liver inflammation due to chronic hepatitis C (HCV-CH). We measured soluble intercellular adhesion molecule (sICAM-1, sCD54), vascular cell adhesion molecule (sVCAM-1, sCD106), E-selectin (sCD62E), as well as interleukin (IL)-1 beta, IL-8, and tumor necrosis factor-alpha (TNF-alpha) concentrations in the serum of 22 patients with HCV-CH in comparison to 20 seronegative healthy volunteers. sICAM-1, sVCAM-1, sCD62E, TNF-alpha, and IL-8 but not IL-1 beta concentrations were significantly elevated in patients. sICAM-1 and sCD62E correlated with TNF-alpha and aspartate amino transferases levels. sICAM-1 correlated with liver lobular inflammation whereas sVCAM-1, sCD62E, and IL-8 correlated with liver fibrosis. Measurement of soluble adhesion molecules may be an easy way to follow liver inflammation and fibrosis during HCV-CH.

Topics: Adult; Aged; Aged, 80 and over; Biomarkers; Cytokines; E-Selectin; Female; Hepatitis C, Chronic; Humans; Intercellular Adhesion Molecule-1; Interleukin-1; Interleukin-8; Liver Cirrhosis; Male; Middle Aged; Tumor Necrosis Factor-alpha; Vascular Cell Adhesion Molecule-1