Objective To examine the levels of interferon-gamma; (INF-gamma;), tumor necrosis factor-alpha; (TNF-alpha;) and interleukin-6(IL-6) in serum of patients with acute uveitis before and after treatment, and to explore the possible roles of those cytokines in the initiation and progression of the uveitis. Methods A series of 75 patients with acute uveitis,and 30 healthy persons from our hospital were investigated. The levels of INF-gamma;, TNF-alpha; and IL-6 in acute phase and convalescent phase were measured by the enzymelinked immunosorbent assay. Result The serum levels of INF-gamma;, TNF-alpha; and IL-6 in acute phase were significantly higher than that of the convalescent phase and the healthy controls (F=65.805/50.418/155.381, P=0.000). A significant negative correlation was found between the serum levels of INF-gamma;, TNF-alpha; and IL-6 in acute phase with their initial visual acuity(r=-0.656, -0.592 and -0.653, Plt;0.01). There was also a positive correlation among the serum levels of INF-gamma;, TNF-alpha; and IL-6(r=0.340, 0.467 and 0.338, Plt;0.05). Conclusions There are high serum levels of INF-gamma;, TNF-alpha; and IL-6 in patients with acute uveitis, and the cytokines levels were decreased after the treatment. The results suggested that the INF-gamma;, TNF-alpha; and IL-6 involved in initiation and progression of uveitis.
This study aims to clarify host factors of IFN treatment in the treatment of chronic hepatitis B (CHB) patients by screening the differentially expressed genes of IFN pathway CHB patients with different response to interferon (IFN) therapy. Three cases were randomly selected in IFN-responding CHB patients (Rs), non-responding CHB patients (NRs) and healthy participants, respectively. The human type I IFN response RT2 profiler PCR array was used to detect the expression levels of IFN-related genes in peripheral blood monocytes (PBMCs) from healthy participants and CHB patients before and after Peg-IFN-α 2a treatment. The results showed that more differentially expressed genes appeared in Rs group than NRs group after IFN treatment. Comparing with healthy participants, IFNG, IL7R, IRF1, and IRF8 were downregulated in both Rs and NRs group before IFN treatment; CXCL10, IFIT1, and IFITM1 were upregulated in the Rs; IL13RA1 and IFI35 were upregulated in the NRs, while IFRD2, IL11RA, IL4R, IRF3, IRF4, PYHIN1, and ADAR were downregulated. The expression of IL15, IFI35 and IFI44 was downregulated by 4.09 (t = 10.58, P < 0.001), 5.59 (t = 3.37, P = 0.028) and 10.83 (t = 2.8, P = 0.049) fold in the Rs group compared with the NRs group, respectively. In conclusion, IFN-response-related gene array is able to evaluate IFN treatment response by detecting IFN-related genes levels in PBMC. High expression of CXCL10, IFIT1 and IFITM1 before treatment may suggest satisfied IFN efficacy, while high expression of IL13RA1, IL15, IFI35 and IFI44 molecules and low expression of IFRD2, IL11RA, IL4R, IRF3, IRF4, PYHIN1 and ADAR molecules may be associated with poor IFN efficacy.
Objective To detect the effects of cytokines on the expression of early growth response gene-1 (Egr-1) in cultured human retinal pigment epithelial (RPE) cells. Methods Immunofluorescence staining, Western blotting and reverse transcription polymerase chain reaction (RT-PCR) were used to detect and quantitatively analyze the expression of Egr-1 protein and mRNA in cultured human RPE cells which were exposed to stimulants, including 20 mu;g/ml lipopolysaccharide (LPS), 40 ng/ml tumor necrosis factor (TNF)-alpha;, 10 U/ml interferon (IFN)gamma;, 30% supernatant of monocyte/macrophage strain (THP1 cells) and the vitreous humor from healthy human eyeballs, for 0, 10, 20, 30, 40 and 60 minutes, respectively. Results The RPE cells stimulated for 0 minute revealed faint green fluorescence of Egr-1 in the cytoplasm. With exposure to the stimulants, the expressionof Egr-1 increased obviously and b green fluorescence was found in cytoplasm in some nuclei of RPE cells. Compared with the untreated RPE cells, after stimulated by 20 mu;g/ml LPS, 40 ng/ml TNFalpha;, 10 U/ml IFNgamma;, 30% supernatant of THP-1 cells and the vitreous humor, the approximate ultimate amplitudes of Egr-1 mRNA enhanced 1.9, 1.3, 14, 1.2, and 1.4 times, respectively; the greatest amplitudes of Egr-1 protein increased 3.4, 1.2, 1.7, 32, and 1.3 times, respectively. Conclusion LPS, TNF-alpha;, IFN-gamma;, supernatant of THP-1 cells and the vitreous humor can upregulate the expression of Egr-1 mRNA and protein in cultured human RPE cells, and induce its nuclear transposition, which suggests the activation of Egr-1.
Objective To investigate the effects of transformin growth factor-beta (TGF-beta;) and interferon-gamma(IFN-gamma;)on collagen synthesis in human retinal pigment epithelial cells(RPE)． Methods TGF-beta;(0.01～10 ng/ml),recombinant IFN-gamma;(100～10000 Ｕ/ml)or a combination of two were added to cultures of RPE and collagen synthesis of the cells were measured by3 H-proline incorporation assay,indirect immunofluorescence staining and dot-blot hybridization. Results TGF-beta; at 10 ng/ml increased cell uptake of 3 H-proline to 130．87% of controls．It intensified Type IV,I and Ⅲ collagen fluorescent staining as well as mRNA expression．IFN-gamma; at 10000 Ｕ/ml caused 54．72% inhibition of 3 H-proline uptake by RPE,and decreased TypeⅣ collagen fluorescent staining as well as mRNA expression of Type Ⅳ,I and Ⅲ collagens. Conclusion TGF-beta; and IFN-gamma; stimulated and inhibited collagen synthesis of human RPE,respectively．The combination of two had antagonistic effects．IFN-gamma; can be used for inhibition of collagen synthesis of RPE. (Chin J Ocul Fundus Dis, 1999, 15: 245-248)
Objective\ To understand the effects of serum of patients with rheumatic heart disease and γ interferon on collagen synthesis by valvular fibroblast cultured in vitro, so as to investigate the possible role of transforming growth factor β in genesis of valvular fibrosis and the possibility of γ interferon used to prevent valvular fibrosis in patient with rheumatic heart disease.\ Methods\ Mitral and aortic valve fibroblasts from 5 patients with rheumatic heart disease were cultured in vitro, the cultured ...
Objective To formulate an evidence-based treatment plan for a patient with hepatitis C after kidney transplantation with combination of interferon-α and ribavirin. Methods Based on an adequate assessment of the patient’ s condition and using the principle of PICO, we searched The Cochrane Library (Issue 1, 2009), PubMed (1995 to March 2009), and CHKD (1995 to 2008.12). Results Eighteen studies were identified including 17 in English (5 case reports, 11 cohort studies, and 1 meta–analysis) and 1 in Chinese. According to the current evidence as well as the patient’ s clinical condition and preference, PEG-IFNα-2b 50 µg /week plus ribavirin 600 mg/day was given to the patient for 6 months. Conclusion Evidence-based approaches help us to prepare the anti-viral therapy plan and will improve the assessment of the efficacy and safety in kidney transplantation.
Objectives To evaluate the clinical effectiveness and safety of combined induction therapy of interferon (IFN) with chemotherapy for survival of the patients with advanced non-small cell lung cancer (NSCLC) by meta-analysis. Methods All clinical trials of addition of IFN plus chemotherapy versus chemotherapy alone for induction therapy to advanced NSCLC patients in MEDLINE (1966-2006), EMBASE (1984-2006.1) and The Cochrane Library (Issue 1,2006) were identified. The references of related studies and Education Books of ASCO and ESMO meeting were handsearched. The quality of included trials was evaluated. Data were extracted by two reviewers independently with a designed extraction form. RevMan 4.2.7 software was used for data analysis. Results Five randomized controlled trials involving 360 patients were included. The pooled result of 3 studies showed that IFN plus chemotherapy induction treatment did not improve 1-year survival rate with RR 0.76, 95%CI 0.46 to 1.26. The pooled result of 5 studies showed that IFN plus chemotherapy induction treatment did not improve response rate with RR 1.40, (0.83 2.34). The pooled result showed that IFN plus chemotherapy induction treatment might significantly increase leukopenia and thrombocytopenia with RR 2.61,95%CI1.70 to 3.99) and RR 4.78,95%CI 1.87 to 12.19 respectively . Conclusion Insufficient data exists to state whether IFN plus chemotherapy induction treatment can improve 1-year survival rate and response rate. IFN plus chemotherapy may increase occurrence of leucopenia and thrombocytopenia. Further studies are warranted.
Interferon regulatory factor 4 (IRF4) is one of the transcription factors in the interferon regulatory factor family. In the normal physiological process, IRF4 protein is a key factor regulating B cell development, such as early B cell development, pre-B cell switch recombination, mature B cell somatic hypermutation, and also a key factor regulating plasma cell differentiation. In addition, in recent years, it has been reported that Irf4 gene abnormalities or abnormal protein expression is closely involved in the occurrence and development of a variety of B cell or plasma cell tumors. This article reviews the physiological role of IRF4 in the differentiation and maturation of B cell or plasma cells, how IRF4 participates in the occurrence and development of B cell or plasma cell tumors, and its potential therapeutic target for B cell or plasma cell tumors.
Objective To investigate the role of IFN-γ in suppressing bleomycin-induced pulmonary fibrosis in rats.Methods Seventy-five SD rats were randomly divided into five groups (15 rats in each group)，ie.a normal group，a bleomycin-induced pulmonary fibrosis model group，a dexamethasone-treated group，a high-dose IFN-γ-treated group (150 000 U/kg) and a low-dose IFN-γ-treated group (50 000 U/kg).Five rats in each group were randomly killed in 7th day，14th day and 28th day after relative treatment respectively，and lung tissue samples were harvested for histopathology study.HE and Masson staining were used to determine the extent of alveolus inflammation and pulmonary fibrosis respectively.Histoimmunochemical method were adapted to determine protein levels of TGF-β1，CTGF，type Ⅰcollagen and type Ⅲ collagen in pulmonary tissues.Results Histopathological study showed that treatment with either dexamethasone or IFN-γ (both high dose and low dose) remarkably meliorated the extent of alveolus inflammation and suppressed pulmonary fibrosis (compared with model group，all Plt;0.05).Histoimmunochemical study suggested that both dexamethasone and IFN-γ could inhibit the expression of TGF-β1，CTGF，type Ⅰand type Ⅲ collagen (compared with model group，all Plt;0.05)，and the suppression of TGF-β1，type Ⅰand type Ⅲ collagen expression was more obvious in high-dose IFN-γ-treated group than those in low-dose group (Plt;0.05).Conclusions INF-γ possesses apparent anti-fibrosis effect that is similar to dexamethasone but with less side effect.Such effect may resulted from reduced production of type Ⅰand type Ⅲ collagen through expression inhibition of cytokines such as TGF-β1 and CTGF.
Objective To evaluate the cost-effectiveness of three LTBI screening strategies: the tuberculin skin test (TST), the T-SPOT.TB and the combination of TST and T-SPOT (TST+T.SPOT), to provide economic evidence for T.SPOT application in China. Methods A decision analysis model evaluated three strategies among a cohort of 1000 tuberculosis (TB) close contacts, using incremental cost-effectiveness of prevention a active TB patient (1 year post contact). Meta analyses were conducted to calculate the key parameters of T.SPOT and TST. The official data or literature was searched and the unaccessible data was to specify other parameters, such as cost, LTBI prevalence, etc. The one-way sensitivity analysis was performed, varying key parameters over a wide range of reasonable values to evaluate the impact of data uncertainties and to determine the robustness of our overall conclusion. Results a) As for the total cost, the TST+T.SPOT strategy (?212 213.81 per 1 000 contacts) cost the least, while the single T.SPOT strategy cost the most; b) Subsequently, the TST+T.SPOT strategy required less contacts to be treated to prevent an active case of TB (8.31) than the single TST strategy (25.67); c) the TST+T.SPOT strategy shared the most cost-effectiveness (?3 063.50 per active TB case prevented) than the single TST or T.SPOT strategy; and d) The results of one-way sensitivity analyses showed that cost-effectiveness values were sensitive to changes in LTBI prevalence (gt;60%), Sen and Spn of TST test (gt;70%), with the single TST being superior to the single T.SPOT. Conclusion The Single T.SPOT strategy enjoys the most cases prevented from active TB, while the TST+S.SPOT strategy is the most cost-effective. The conclusion is sensitive to a few parameters, such as LTBI prevalence, but the TST+T.SPOT strategy is always the best.