Baseline immune activation as a risk factor for the onset of depression during interferon-alpha treatment.

BACKGROUND: Major depression has been associated cross-sectionally with increased cell-mediated immune activation but causality has been difficult to establish. This study prospectively investigated the hypothesis that baseline level of immune activation predicts the development of depression during interferon-alpha (IFN-alpha) treatment. METHODS: Sixteen hepatitis C patients without psychiatric disorder underwent IFN-alpha treatment. Proinflammatory and anti-inflammatory cytokines were determined before starting treatment. Presence of a major depressive disorder (MDD) was assessed at baseline and several times during treatment. RESULTS: Baseline soluble interleukin-2 receptor (sIL-2r), interleukin-6 (IL-6), and interleukin-10 (IL-10) concentrations were significantly increased in the five subjects that developed MDD during treatment compared with those that did not, with standardized effect sizes of 1.08, 1.16, and 1.25, respectively, controlling for marijuana use, cigarette smoking, and baseline level of depressive symptoms. CONCLUSIONS: Results suggest that increased immune activation, rather than an epiphenomenon, is a causal risk factor for the development of MDD.     

慢性丙肝患者干扰素治疗前后血清细胞因子的变化

目的 :探讨细胞因子在慢性丙型肝炎发病机制中的作用。方法:2 0例慢性丙型肝炎患者应用干扰素联合利巴韦林抗病毒治疗 2 4周。于治疗前后用 EL ISA法检测血清 IL- 2、IFN- γ、IL- 4、IL- 10水平 ,同时检测生化和病毒指标并观察不良反应。结果:抗病毒治疗后 IL- 2、IFN- γ、IL- 4、IL- 10水平发生了明显变化。与治疗前比较 ,IL- 2、IFN- γ水平逐渐升高 ,IL- 4、IL- 10水平逐渐降低 ,其中 IL- 2、IL- 10水平变化具有统计学意义 (P<0 .0 1)。对干扰素完全应答者 15例 ,IL- 2、IL- 10水平变化具有统计学意义 (P<0 .0 5 ) ;无应答者 5例 ,IL- 2、IFN- γ、IL- 4、IL- 10水平变化无统计学意义 (P >0 .0 5 )。抗病毒治疗过程中无严重不良反应。 结论:IL - 2、IL - 4、IL - 10、IFN-γ共同参与了丙型肝炎的发病。干扰素联合利巴韦林通过调整机体的免疫状态而发挥抗病毒效应 ,IL - 2、IL - 10可以作为预测抗病毒疗效的指标之一。     

Cutaneous, pulmonary and hepatic sarcoidosis associated with autoimmune complications during interferon-alpha treatment for hepatitis C virus infection

A patient with hepatitis C virus (HCV) infection was diagnosed with cutaneous, pulmonary and hepatic sarcoidosis following interferon alpha therapy. There are only a few cases of sarcoidosis associated with this treatment. This is the first case who not only developed sarcoidosis, but also autoimmune hypothyroidism and thrombocytopenia during interferon alpha therapy due to the immunomodulatory effects of the drug.     

Interferon-alpha and dexamethasone inhibit adhesion of T cells to endothelial cells and synovial cells

We investigated whether interferon-gamma (IFN-gamma), interferon-alpha (IFN-alpha) and glucocorticoids affected the adhesion of T cells to human umbilical endothelial cells or human synovial cells. About 30% of peripheral blood T cells could bind to unstimulated endothelial cells, but only a few T cells could bind to unstimulated synovial cells. When both endothelial cells and synovial cells were cultured with recombinant IFN-gamma (rIFN-gamma), the percentage of T cell binding to both types of cells increased in a dose-dependent manner. rIFN-alpha and dexamethasone blocked the T cell binding to unstimulated endothelial cells. Furthermore, rIFN-alpha and dexamethasone suppressed T cell binding to both endothelial cells and synovial cells stimulated by IFN-gamma, and also inhibited intercellular adhesion molecule-1 (ICAM-1) expression on both endothelial cells and synovial cells stimulated by IFN-gamma. These results suggest that IFN-alpha and glucocorticoids may inhibit T cell binding to endothelial cells or synovial cells by modulating adhesion molecule expression on these cells.     

Prevalence of viral infection markers by polymerase chain reaction amplification and interferon-alpha measurements among patients undergoing lumbar puncture in an emergency department

Aseptic meningitis is a frequent diagnosis in emergency departments. Nevertheless, viral investigations are not carried out currently and the viral etiology in adult population has not been studied extensively. We conducted a prospective study including all consecutive patients undergoing lumbar puncture during a 15 months period in an adult emergency department. Bloody and purulent cerebrospinal fluid (CSF) were excluded. The main tests undertaken were: CSF genomic amplification by the polymerase chain reaction (PCR) for neurotropic viruses and serum and CSF interferon-alpha (IFN-alpha) measurements. Among 194 patients included, 45 had and 149 did not have aseptic meningitis. Of 45 patients with aseptic meningitis, 10 had alternative non-virological final diagnosis, and 35/45 were presumed to have neurological disorders of viral origin. Patients (27/35) completed virological analysis: 21/27 (78%) had either positive viral PCR (enterovirus: 8 patients, Varicella zoster virus (VZV): 5, Epstein-Barr virus (EBV): 2, herpes simplex virus (HSV): 1, human herpes virus 6: 1) or only raised serum or CSF IFN-alpha (4 patients). Overall, 59% of patients with a positive viral PCR had either CSF or serum raised IFN-alpha. Twentyone patients without meningitis had either positive viral PCR (enterovirus: 3 patients) or only high serum IFN-alpha level (18 patients). In the setting of aseptic meningitis diagnosed in an adult emergency department, viruses are the most common agents encountered, with enterovirus and VZV as the two main etiological agents. Current CSF viral genome amplification and IFN-alpha measurement are informative and could be useful to confirm the viral origin of various neurological disorders, although the sensitivity and specificity of IFN-alpha measurement for the diagnosis of viral infection need further confirmation.     

Common variable immunodeficiency (CVID) and MxA-protein expression in blood leucocytes.

The underlying immunopathogenic mechanism of CVID has been suspected to involve a chronic viral infection or an autoimmune condition. However, formal proof of viral infection is lacking. Measurement of MxA-protein in leucocyte lysates is a sensitive test for evaluating the activation of the host's interferon system. Both viral infections and autoimmune diseases such as systemic lupus erythematosus (SLE) strongly induce MxA-protein in peripheral leucocytes. We therefore examined 15 patients with longlasting hypogammaglobulinaemia for MxA-protein induction in vivo: 13 patients suffered from CVID, one from hyper-IgM syndrome, and one patient had chronic B lymphocytic leukaemia associated with immunoglobulin deficiency and chronic papilloma virus infection (condylomata accuminata). Only the latter patient exhibited a strong MxA-protein expression; two CVID patients were borderline positive, and the remaining 12 patients including the hyper-IgM syndrome were MxA-protein-negative. There was no relationship between MxA expression and low CD4/CD8 ratios or increased CD8/CD57+ T cell counts, although both conditions are often observed in CVID as well as in chronic viral infections. When exposed in vitro to interferon-alpha (IFN-alpha), peripheral blood leucocytes of four MxA-negative patients were capable of producing normal amounts of MxA-protein. Taken together, these results argue against a viral or autoimmune pathogenesis of CVID.     

TNF-α和IFN-α对淋巴细胞迁移至小鼠皮肤区的影响

目的　体内观察TNF -α和IFN -α两种细胞因子对淋巴细胞迁移至小鼠皮肤区的影响。方法　以近交系BALB/C小鼠为实验动物 ,皮内注射细胞因子 ,尾静脉输注标记的淋巴细胞 ,然后切取注射区皮块 ,制样后行乳化计数测量。测量值计算后转化成细胞浓度因子 (CCF) ,用CCF值反应淋巴细胞迁移的水平。结果　TNF -α和IFN -α注射区CCF值均高于对照(P <0 0 1) ;且TNF -α与IFN -α联合应用的CCF值是TNF -α和IFN -α各自应用之和的 137%。结论　TNF -α及IFN-α可以体内诱导淋巴细胞迁移至小鼠皮肤区内。     

Acute fungal thyroiditis in a patient with acute myelogenous leukaemia.

Acute suppurative thyroiditis of any origin is uncommon, but fungal infections of the gland are particularly rare. Haematogenous spread is the usual route of infection. We here present the case of a recently encountered patient with neutropenic fever and Candida thyroiditis. Fine-needle aspiration biopsy greatly aided the diagnosis. In immunocompromised patients, the specimens should be treated with special stains to detect the presence of opportunistic organisms; if any are found, appropriate therapy should be initiated.     

Premature vascular damage in systemic lupus erythematosus

Systemic lupus erythematosus (SLE) is a disease associated with a striking increase in the risk of premature cardiovascular (CV) complications due to accelerated atherosclerosis. Traditional CV risk factors seem to be less important predictors of CV events than the presence of active SLE. Immune dysregulation characteristic of lupus appears to play the dominant role in atherogenesis. While both SLE-specific and non-specific mechanisms have been proposed to play a prominent role in the induction of premature vascular damage in this disease, the exact etiology remains unclear. We have proposed that an imbalance between vascular damage and repair likely induced by Interferon-α could play a prominent role in the induction of accelerated atherosclerosis in SLE. This review summarizes some of the proposed mechanisms that may promote accelerated vascular damage in lupus and explores potential targets for CV risk prevention in this patient population.     

干扰素联合病毒唑对慢性丙肝患者正负链HCV RNA的影响

目的探讨干扰素联合病毒唑对正、负链丙型肝炎病毒 RNA(HCV RNA)的影响.方法 23例患者,依据 HCV RNA 及抗-HCV 阳性,肝功能反复不正常,病程持续1年以上,其他肝炎病毒标志阴性,被诊断为慢性丙型肝炎(CHC).其中,13例接受联合抗病毒治疗,即α-干扰素300万 U,皮下注射,每周3次,治疗3个月;和病毒唑1g,于干扰素治疗的第1个月,同时静脉滴注,1次/d,治疗1个月.10例单用干扰素治疗3个月(用法同上).作为对照.其血清及周围血单核细胞(PBMCs)中正、负链 HCV RNA 用套式反转录—聚合酶链反应技术检测.结果联合抗病毒组中,9例(69.23%)异常的 ALT 降至正常,5例于治疗停止后第24周复发,4例为完全应答者;而单用干扰素组,分别为6例(60%)、4例(66.67%)和2例(33.335).两组间无明显差异(P>0.05).治疗结束时,联合抗病毒组的血清正链阳性率由92.31%降至38.46%(P<0.05),PBMCs 的负链阳性率由76.92%降至38.46%(P<0.05);而单用干扰素组,分别为100%降至50%(P<0.05)和90%降至40%(P<0.05).但组间无差异(P>0.05).复发见于治疗前后 PBMCs 中正链 HCVRNA 持续阳性的患者.结论病毒唑似不能增加干扰素的疗效.血清 HCV RNA 的阴转并不意味着 HCV 的完全清除,因而用它判断疗效及病情转归有一定的局限性.因此,同时检测血清及 PBMCs 中正、负链 HCV RNA,具有重要的临床意义.