الفهرس 
InterferonsOnly 14 pages are availabe for public view
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Abstract
The chronic hepatitis C virus (HCV) infects approximately 130 million people world wide .It is estimated that approximately 15% of HCV- infected individuals eliminates the virus spontaneously, that 25% develop a mild form of the disease and that 60% develop the chronic progressive form .
The elimination or persistence of HCV infection depends on the balance between the effectiveness, specificity and rapidity of the innate and adaptive immune responses, as well as on the HCV replication rate.
The innate immune response to HCV is responsible for the activation of cytokines such as interferons (IFNs) which activate antiviral proteins that inhibit the replication of the virus while the adaptive immune response to HCV neutralizes viral particles and destroys infected cells. Various studies have suggested that after HCV enters the host cell, E2 glycoprotein inhibits cytotoxicity and the production of interferon gamma (IFN- γ) by NK cells.
IFNs belong to the large class of glycoproteins known as cytokines. Although they are named after their ability to ”interfere” with viral replication within host cells, IFNs have other functions: they activate immune cells, such as natural killer cells and macrophages; they increase recognition of infection or tumor cells by up-regulating antigen presentation to T lymphocytes; and they increase the ability of uninfected host cells to resist new infection by virus. Certain host symptoms, such as aching muscles and fever, are related to the production of IFNs during infection.
About ten distinct IFNs have been identified in mammals; seven of these have been described for humans. They are typically divided based on the type of receptor through which they signal among three IFN classes: Interferon type I: All type I IFNs bind to a specific cell surface receptor complex known as the IFN-α receptor (IFNAR) that consists of IFNAR1 and IFNAR2 chains. The type I interferons present in humans are IFN-α, IFN-β and IFN-ω. Interferon type II: Binds to IFNGR. In humans this is IFN-γ.Interferon type III: Signal through a receptor complex consisting of IL10R2 (also called CRF2-4) and IFNLR1 (also called CRF2-12). Acceptance of this classification is less universal than that of type I and type II, and unlike the other two, it is not currently included in Medical Subject Headings.
Interferons produce a variety of biological effects on cells.They induce resistance to virus proliferation, inhibit cell growth, modify cell structure and differentiation, stimulate some immune functions and inhibit others. However, the different interferon species may vary in their mechanism of action and, hence, in their relative efficiency for inducing each of the effects .For example , IFN-γ appears to show stronger immunoregulatory and growth inhibitory effects than antiviral effects, but this inversed for IFN-α/β which show stronger antiviral effects .On the other hand IFN-λ induced antiviral activity in fewer cell lines and more weakly than IFNs .However, IFN-λ is capable of signaling through almost all STAT molecules and so it is possible that it may have novel immunoregulatory functions in addition to antiviral ones .
HCV can be cleared without humoral immune responses in immunocompromised (e.g., hypogammaglobulinemic) patients. In immunocompetent patients, neutralizing antibodies appear late and are isolate specific, which necessitates the generation of viral particles with patient-specific HCV sequences to detect these antibodies in invitro neutralization assays.
In contrast to antibodies, HCV-specific T cells are critical for HCV clearance .The decrease of viral titer coincides precisely with the appearance of HCV-specific T cells and IFN-γ expression in the liver, which suggests that viral clearance is T cell mediated. Whether IFN-γ is directly involved in HCV clearance or whether it is just a marker for other T cell functions has not yet been determined. Direct antiviral functions would be consistent with the observation that IFN-γ–mediated inhibition of sub genomic and genomic HCV RNAs is about 100- to 1,000-fold more effective than cytotoxicity.
The production of inflammatory cytokines with antiviral activity such as IFN-γ is an important but often underestimated way by which the immune system fights viral infections .IFN-γ inhibits HCV replication in infected hepatocytes. Recent studies in chimpanzees and humans indicate that a vigorous and multispecific T-cell response in the early phase of HCV infection favors subsequent viral clearance, whereas a weak and focused response is associated with virus persistence. It is, therefore, tempting to speculate that infiltrating or intrahepatic immune cells do not primarily kill infected hepatocytes but rather secrete IFN-γ to control HCV replication in a noncytolytic manner.
The aim of present study was to determine the serum levels of IFN- γ in HCV infection in different clinical setting.
In present study, we quantitated the level of IFN-γ using ELISA technique to estimate the level of interferons in different clinical outcomes of HCV infection in health care workers.
HCWs were screened for HCV Ab by ELISA technique and HCV RNA by Real-Time PCR (RT-PCR).According to the results of HCV RNA and HCV Ab, subjects were divided into three groups:
group I (Chronic hepatitis C patients):
Consisted of 26 chronic HCV patients (positive for both anti-HCV and HCV RNA).They were 14 males (53.8 %) and 12 females (46.2%).
group II (Spontaneous HCV Resolvers):
Consisted of 7 HCWs who were positive for anti-HCVAb and negative for HCV-RNA. They were 2 males (28.5 % ) and 5 females( 71.4 %).
group III (Healthy group):
Consisted of 21 HCWS who were negative for both anti-HCV and HCV- RNA .They were 8 males ( 33.3 %) and 13 females( 66.7%) .
Exclusion criteria for groupI included IFNs or ribavirin therapy.
All subjects included in the study were subjected to full history taking, questionnaire investigating different risk factors for infection with HCV, ALT level anti-HCV and HCV RNA load were done as routine investigation for all the subjects .In the present study, the serum levels of IFN-gamma were significantly decreased in chronic hepatitis C virus (HCV) in comparison to healthy individuals ,suggesting that low IFN-γ may play a role in pathogenesis of HCV.On the other hand ,no significant difference in the percentage of CD8+ T cell was found between chronic HCV and recovered HCVpatient .The study of HCV-specific CD8+ T cell may be more conclusive.
Many factors that may have potentially affected our results cannot be evaluated. These include HCV genotype and species diversity, duration of HCV infection, age when first infected and severity of hepatitis by histologic analysis.Interferon gamma possesses marked immunomodulating activity. And as cell immunity seems to be involved in chronic hepatitis C virus (HCV), study of the events regulated by IFN-gamma may be useful in evaluating the host’s immunological response.