The increased interleukin-13 in patients with systemic lupus erythematosus: relations to other Th1-, Th2-related cytokines and clinical findings.

The levels of interleukin-13 (IL-13) in patients with systemic lupus erythematosus (SLE) were examined and related to other Th1-/Th2- related cytokines, clinical manifestations and other markers. Serum levels of IL-13 and other cytokines, soluble markers were measured by enzyme-linked immunosorbent assay (ELISA). Patients with active SLE had a significantly increased level of IL-13. Most patients with high levels of IL-13 had higher levels of IL-6, and some patients had high levels of gammaIFN. These patients were divided into two groups according to the patterns of these increased cytokines; one with a high level of only Th2 related cytokines (IL-13 or IL-6) and another with high levels of both Th2 related and Th1 related cytokines (gammaIFN or IL-2). The latter patients had high levels of soluble CD8 and CD23, and some of them had hemolytic anemia or pulmonary involvement, while most of the former patients had nephropathy. Thus, in SLE, the levels of IL-13 were increased, and the heterogeneity of increased Th2- and Th1-related cytokines was related to that of activation markers and clinical manifestations.     

Increased IL-12 and decreased IL-33 serum levels are associated with increased Th1 and suppressed Th2 cytokine profile in patients with diabetic nephropathy (CURES-134)

The role played by recently discovered novel cytokine IL-33 in controlling T-helper (Th)1 and Th2 cytokines under conditions of diabetic nephropathy (DN) is less well studied. In the present study, we estimated the levels of IL-33 along with both Th1 and Th2 cytokines in the serum of normal glucose tolerant (NGT), diabetic subjects with (DN) or without nephropathy (DM) and correlated it with the clinical risk factors of diabetes and nephropathy. 222 study subjects were recruited from the Chennai Urban Rural Epidemiology Study (CURES): 61 NGT, 79 DM and 82 DN. IL-33 level was estimated by ELISA while other Th1 (IL-12, IFN-gamma and IL-2) and Th2 (IL-4, IL-5 and IL-13) cytokines were measured using a Bio-plex bead assay. DM subjects showed a mixed Th1-Th2 profile (increased IFN-g, IL-12, IL-4 and IL-13 and decreased IL-33) while DN subjects showed enhanced Th1 profile (increased IFN-g, IL-2 and IL-12) with suppression of Th2 cytokine (decreased IL-33 and IL-13). The IL-33 levels showed a serial decline with increasing severity of insulin resistance and microalbuminuria. DN was associated with enhanced Th1 response and suppression of Th2 responses which might be due to inreased levels of IL-12 and decreased levels of IL-33 cytokines respectively.     

Adult Still's disease reflects a Th2 rather than a Th1 cytokine profile

Adult Still's disease (ASD) is a chronic multisystemic disease. Extraordinarily high serum levels of IL-18 in ASD patients have been described, whereas the mechanism remains to be clarified. This study aimed to evaluate proinflammatory cytokines and to consider their pathological roles. In patients with rheumatic diseases (n = 151), blood samples were taken at the active phase and the serum levels of IL-18 and other proinflammatory cytokines were measured by ELISA. The extra-high levels of IL-18 were confirmed selectively in ASD patients (n = 10). In the active phase of ASD patients, the levels of IL-6 were elevated accordingly, but IL-1beta and TNF-alpha were undetectable. As to Th1-Th2 cytokines, the levels of IL-4 and IL-13, but not INF-gamma, IL-12, or IL-2, were elevated in all ASD patients examined. Moreover, the serum levels of IL-18 showed a good correlation with those of IL-4, suggesting that ASD reflects a Th2 rather than a Th1 cytokine profile.     

Th1 and Th1-inducing cytokines in Salmonella infection

Thl and Thl-inducing cytokines and T cell responses were investigated in human salmonellosis. Serum IFN-gamma, IL-12 and IL-18 levels were increased significantly in patients with salmonellosis. The increase in serum IL-15 and IL-18 levels was more significant and prolonged in patients with the systemic form of salmonellosis than in those with the gastroenteric form. The serum IFN-gamma level was correlated significantly with IL-12 and IL18 levels, and the IL-15 level was correlated significantly with IL-18. Upon stimulation with Salmonella in vitro, mononuclear cells from salmonellosis patients produced significantly higher amounts of IFN-gamma and IL-12 compared with those from healthy controls. Anti-IL-12 moAb or anti-IL18 MoAb significantly inhibited Salmonella-induced IFN-gamma production in vitro. gamma delta T cells expressed significantly higher levels of IFN-gamma mRNA in salmonellosis patients than in healthy controls. The results suggest that Th1-inducing cytokines appear to be involved in the in vivo response against Salmonella infection, promoting IFN-gamma production by alpha beta and gamma delta T cells which plays a protective role against Salmonella.     

The expression and significance of intracellular T helper cytokines in systemic lupus erythematosus

To analyze the Th1 and Th2 paradigm of peripheral T helper cells in patients with systemic lupus erythematosus (SLE). The intracellular Th1 and Th2 cytokines were analyzed in fresh blood T cells from 20 SLE patients who had not yet received any treatment. Th1 and Th2 cells were quantitated based on their intracellular cytokine content as assessed by flow cytometry. Cytokine expressions were correlated with clinical features, laboratory findings, and disease activities. There was no difference in the expression of intracellular IFN-y, or IL-4 between SLE patients and healthy controls. However, the IL-2 and IL-10 levels were significantly higher and lower respectively in the lupus patients than in the control group. In addition, patients with arthritis had higher IFN-gamma expression than patients without arthritis. Moreover, patients with serositis or CNS involvement had higher IL-4 expression than in patients without these manifestations. There was no correlation between the SLEDAI scores and the cytokine expression levels. However, patients with serum anti-ds DNA antibodies had higher IL-10 levels than in those without these antibodies. The present study demonstrates that a Th1 pattern of intracellular cytokines predominates in patients with SLE prior to treatment. The pattern of particular intracellular T cell cytokines may suggest specific clinical manifestations and disease progression of SLE.     

Th17细胞在系统性红斑狼疮免疫炎症反应中的作用机制研究

目的从Th17/Treg、IL-17及RORγt mRNA表达3方面进行研究,探讨Th17细胞在SLE免疫炎症反应中的作用机制。方法研究对象为26例活动期SLE患者、16例非活动期SLE患者和20例正常对照,采用细胞内染色流式细胞术检测Th17/Treg,ELISA法检测IL-17及RT-PCR法检测RORγt mRNA表达,并探讨它们与SLE疾病活动性的关系。结果活动期SLE患者组Th17/Treg、IL-17及RORγt mRNA表达水平显著高于非活动期及正常对照组;非活动期SLE患者组RORγt mRNA表达显著高于正常对照组,但两组间Th17/Treg、IL-17水平无显著差异。SLE患者Th17/Treg、IL-17及RORγt mRNA表达水平均与和SLEDAI呈正相关。结论 SLE患者存在着Th17细胞高表达现象,阻断Th17细胞分化的上游或下游均可能减轻SLE的免疫炎症反应而达到治疗SLE的目的。     

A switch towards Th2 during serological rebound in children with congenital toxoplasmosis.

Serological rebounds occur frequently in patients with congenital toxoplasmosis, but remain poorly understood. A link between Th1 and Th2 cytokines and the pathophysiology of infectious diseases has been reported. Production of interferon-gamma (IFN-gamma) and IL-4 in supernatants of whole blood after in vitro specific Toxoplasma gondii stimulation and serum-specific IgE levels were studied in 31 congenitally infected children. IFN-gamma was produced at higher levels by lymphocytes from children with stable congenital toxoplasmosis (n = 18) than from children showing serological rebound (n = 13) (P < 0.04). Conversely, supernatants from children with serological rebound showed higher levels of IL-4 than those from children with stable congenital toxoplasmosis (P < 0.03). The polarized Th2 response was confirmed by a greater (IL-4:IFN-gamma) x 100 ratio (P < 0.0001) and production of T. gondii-specific IgE in six out of 13 children showing serological rebound. These results suggest a role of Th2 cytokines in destabilization of congenital toxoplasmosis and perhaps in local reactivation of the parasite.     

系统性红斑狼疮患者的Th细胞亚群平衡失调的初步研究

为分析Th亚群平衡失调在系统性红斑狼疮 (SLE )发生发展中的变化特点 ,以ELISA法检测血清IL 10、IL 12水平 ,以细胞内细胞因子的流式细胞术检测SLE患者PBMC的不同Th细胞亚群分泌细胞因子的变化特点 ,应用三色荧光标记技术分析Th1/Th2细胞表型。结果显示 :SLE患者血清IL 10水平显著高于正常人 ,而IL 12呈低水平表达。SLE患者CD4 + IFN γ IL 10 + 细胞亚群百分率显著高于正常人 ,IFN γ+ IL 10 与IFN γ IL 10 + 细胞亚群的比值明显降低 ,IFN γ+ IL 10 + 双阳性的CD4 + T细胞亦显著增多。SLE患者的CD4 + CCR5 CCR3+ 细胞亚群百分率与正常人比较显著升高 ,CD4 + CCR5 + CCR3 细胞亚群与正常人比较 ,示发现有显著差异 ,CD4 + CCR5 + CCR3 /CD4 + CCR3+ CCR5 比值显著低于正常对照组。这些结果提示 :SLE高水平IL 10与IL 12的低水平表达呈负相关 ;患者体内分泌IL 10的Th细胞数增多 ;Th细胞表面趋化因子受体的表达提示SLE存在CCR5 CCR3+ 细胞亚群的优势活化、数量增多 ,CCR5 + CCR3 /CCR3+ CCR5 细胞比例失调 ,从而导致免疫网络平衡被破坏。     

Role of Th1 and Th2 cytokines in immune response to uncomplicated Plasmodium falciparum malaria

The relative balance between Th1 and Th2 cytokines appears crucial, since the role of cytokines has been evaluated in several studies by comparison of clinically heterogeneous groups of patients. The aim of this study is to determine the role of proinflammatory Th1 cytokines, interleukin-12 (IL-12) and gamma interferon (IFN-gamma), and anti-inflammatory Th2 cytokines, IL-4 and IL-10, in a homogeneous group of patients with uncomplicated Plasmodium falciparum malaria. Levels of IL-12, IFN-gamma, Il-4, and IL-10 in serum for 20 adult patients and 15 healthy control subjects were determined by an immunoenzymatic assay. Serum levels of Th1 cytokines, IL-12 (8.6 +/- 2.8 pg/ml; controls, 3.2 +/- 0.7 pg/ml) and IFN-gamma (39.2 +/- 67.6 pg/ml; controls, 8.4 +/- 6.3 pg/ml), were significantly increased at admission; 3 days later, levels of IL-12 in serum remained significantly high (8.8 +/- 2.6 pg/ml), whereas IFN-gamma levels returned to control values. The anti-inflammatory response of Th2 cytokines (IL-10 and IL-4) was distinct. Levels of IL-10 in serum were not significantly increased at day 0 and day 3 (306.6 +/- 200.4 pg/ml and 56.6 +/- 38.4 pg/ml, respectively; controls, 17.4 +/- 9.0 pg/ml). In contrast, levels of IL-4 in serum were not increased on admission (3.4 +/- 1.2 pg/ml; controls, 2.4 +/- 0.8 pg/ml), but at day 3 a moderate and significant increase of IL-4 levels was observed (4.5 +/- 1.7 pg/ml). In conclusion, the increase of Th1 cytokine IL-12 and IFN-gamma levels during the acute phase of uncomplicated P. falciparum malaria may reflect an early and effective immune response regulated by proinflammatory Th1 cytokines, and in particular IFN-gamma may play a role in limiting progression from uncomplicated malaria to severe and life-threatening complications.     

In vitro responsiveness to IL-18 in combination with IL-12 or IL-2 by PBMC from patients with bronchial asthma and atopic dermatitis

Interleukin (IL)-18 is a proinflammatory cytokine and is now recognized as an important regulator of both helper T cells (Th) 1 and 2 cytokine production. An increased IL-18 secretion has been reported in patients with allergic disorders. It is predominantly produced by activated macrophages, and synergizes with IL-12 and IL-2 to induce IFN-gamma synthesis, thereby promoting Th1 cytokine response. Paradoxically, IL-18, by itself, strongly induces immunoglobulin (Ig) E and allergic inflammation, indicating a role for IL-18 in promoting Th2 response. We investigated the inducing effect in vitro of combining IL-18 and Il-12 or Il-2 on Th1- and Th2-type cytokines production by peripheral blood mononuclear cells (PBMC) from patients with allergic diseases. PBMC derived from 44 allergic patients [23 bronchial asthma (BA) and 21 atopic dermatitis (AD)] and 20 healthy controls were cultured with IL-18 in the presence of phytohemagglutinin (PHA) and IL-12 or IL-2. The levels of IFN-gamma, IL-13, and IL-4 in the culture supernatants were measured using enzymatic immunoassaying. IFN-gamma production was detected in all cultures from nonallergic controls stimulated with IL-18 in the presence of IL-12; however, the results for five BA patients and five AD patients were under the detection limit for IFN-gamma. In collaboration with IL-2, IL-18 was able to induce IFN-gamma production by PBMCs from all nonallergic controls and all allergic patients, with the exception of one AD patient. Synergistic induction of IL-13 production was found in cultures with IL-18 + IL-2, and the IL-13 induction was significantly increased in BA patients when compared with that in nonallergic controls (P = 0.006). The stimulation by IL-18, even in combination with IL-2, failed to induce IL-4 production by PBMC from both nonallergic controls and allergic patients. Although the induction of IFN-gamma by IL-18 + IL-12 was impaired in around a quarter of the allergic patients, the impairment of the IFN-gamma production was completely restored by IL-2 in the presence of IL-18. Thus, IL-18 enhances IFN-gamma production through an IL-12-dependent pathway and exhibits synergism when combined with IL-2 in terms of enhanced IL-13 and IFN-gamma production, suggesting the involvement of IL-18/IL-12/IL-2 pathway in modulating Th1/Th2 cytokine response.     

High Th1-type cytokine serum levels in patients with infectious mononucleosis

Most adults are asymptomatically infected with Epstein-Barr virus (EBV). Primary EBV infection is commonly associated with acute infectious mononucleosis (IM). T cell immune activation plays an important role in EBV-associated diseases. IM shows a mainly Th1-type profile, so Th1-type cytokines such as interleukin-2 (IL-2), interferon-gamma (IFN-gamma), and lymphotoxin (LT) are moderately enhanced. We measured IL-2 and IFN-gamma in serum during acute phase of the disease and during convalescence. Sera were collected from 23 IM patients, 13 patients with similar clinical manifestations but without IM, and 10 healthy donors. The levels of IL-2, IFN-gamma and IL-12 were significantly higher in patients with acute IM than in healthy individuals. IL-2, IFN-gamma and IL-12 decreased during convalescence. These three cytokines may be useful as sensitive markers of IM during severe illness and its later phases.     

Hyperproduction of IL-23 and IL-17 in patients with systemic lupus erythematosus: implications for Th17-mediated inflammation in auto-immunity

IL-23-dependent IL-17-producing T helper (Th) lymphocytes are associated with autoimmunity. We investigated the immunopathological mechanisms for activation of Th17 cells of patients with systemic lupus erythematosus (SLE). Concentration of cytokines/chemokine in plasma and culture supernatant from SLE patients and healthy controls were measured by ELISA or flow cytometry. Plasma IL-12, IL-17, IL-23 and CXCL10 concentrations and the number of Th17 cells were significantly elevated in SLE patients than control subjects (both p < 0.05). Elevated IL-12, IL-17 and CXCL10 concentrations correlated positively and significantly with SLEDAI (all p < 0.05). Plasma IL-12 and IL-17 showed significant and positive correlation with plasma Th1 chemokine CXCL10 concentration in SLE patients (all p < 0.05). Ex vivo inductions of IL-17 by IL-23 or IL-18 from co-stimulated lymphocytes were significantly higher in SLE patients than controls (all p < 0.05). The activated IL-23/IL-17 axis is important for the inflammatory immunity in SLE.     

Elevated interleukin-18 levels in bronchoalveolar lavage fluid of patients with eosinophilic pneumonia

BACKGROUND: Interleukin (IL)-18 can induce Th2 cytokine production particularly in collaboration with IL-2. Accumulation of Th2 cells and increased levels of Th2 cytokines are found in bronchoalveolar lavage fluid (BALF) from patients with eosinophilic pneumonia (EP). To evaluate the role of IL-18 in the pathogenesis of EP, we measured the concentration of IL-2, IL-12, IL-18, and Th2 cytokines in BALF from patients with EP. METHODS: The concentrations of interferon (IFN)-gamma, IL-2, IL-5, IL-10, IL-12, IL-13, and IL-18 in BALF were measured in patients with idiopathic acute eosinophilic pneumonia (AEP), with idiopathic chronic eosinophilic pneumonia (CEP), with sarcoidosis and healthy volunteers (HV). RESULTS: The BALF concentrations of Th2 cytokines, IL-5, IL-10, and IL-13, were higher in patients with EP than in sarcoidosis and control. The IL-2 level in BALF was higher in EP than in sarcoidosis and control. The IL-18 and IL-12 (p40 + p70) levels were higher in patients with EP than sarcoidosis, while the level of IL-12 (p70) was below the detection limit in patients with EP. There was a significant correlation between IL-2 level and both IL-5 and IL-13 in BALF of patients with EP. CONCLUSIONS: Our findings suggest that IL-18 may contribute to Th2 cytokine-dominant responses in patients with EP in collaboration with IL-2.     

Nickel-induced IL-10 down-regulates Th1- but not Th2-type cytokine responses to the contact allergen nickel

Whereas the involvement of Th1- and Th2-type cytokines in contact allergy to nickel (Ni) is well documented, the role of the regulatory cytokine IL-10 is less clear. We therefore investigated the impact of IL-10 on Ni-induced Th1- (IFN-gamma) and Th2-type (IL-4 and IL-13) cytokine responses in human peripheral blood mononuclear cells (PBMC). PBMC from 15 blood donors with reactivity to Ni (Ni-PBMC) and 8 control donors devoid of reactivity (control PBMC) were stimulated with Ni and the frequency of cytokine-producing cells and the levels of secreted cytokines were analysed by ELISpot (IL-4, IL-13 and IFN-gamma) and ELISA (IL-10, IL-13 and IFN-gamma), respectively. The Ni-induced response was further assessed in the presence of recombinant IL-10 (rIL-10) or neutralizing antibody to IL-10 and the phenotype of the Ni-specific cytokine-producing cells regulated by IL-10 was determined by cell depletion experiments. Ni induced IL-10 production in Ni-PBMC (mean, (range); 33.1 pg/ml (0-93.4 pg/ml)) but not control PBMC (2.2 pg/ml (0-14.9 pg/ml)) (P = 0.002). Ni also induced significant production of IL-4, IL-13 and IFN-gamma that correlated with the IL-10 response. Addition of rIL-10 down-regulated the Ni-induced production of all cytokines but with a more pronounced effect on IFN-gamma. However, neutralization of Ni-induced IL-10 enhanced the levels of IFN-gamma induced by Ni (P = 0.004) but did not affect the number of IFN-gamma-producing cells or the production of other cytokines. Cell depletion experiments suggested that the Ni-specific IFN-gamma (and Th2-type cytokine) producing cells were CD4(+) T cells. The impact of IL-10 on Ni-induced IFN-gamma responses by CD4(+) T cells suggests that an important role of IL-10 in vivo is to counteract the allergic reactions mediated by Th1-type cytokines.     

The Th1/Th2 cytokine balance changes with the progress of the immunopathological lesion of Sjogren's syndrome

Expression of type-1 and type-2 cytokines at the mRNA level in labial salivary glands (LSG) of patients with Sjogren's syndrome (SS), as reported by several groups, have generated conflicting results. In the present study we have directly examined the production of IL-4, IL-13 and IFN-gamma by lymphocytes infiltrating the LSG of 44 consecutive patients referred for SS evaluation. Cytokines production was evaluated following in vitro culture of LSG in the presence of IL-2. IFN-gamma and IL-13 were detected in the majority of SN (24/44 and 26/44, respectively) while IL-4 was present in 5/44 SN. The presence of IFN-gamma was significantly higher in SS patients, as opposed to patients who did not fulfil the criteria for SS (P < 0.01). In addition, almost all cultured lymphocytes expressed mRNA for IFN-gamma (17/19 cultures) and IL-13 (18/19) while IL-4 mRNA was also expressed at high frequency (14/19 cultures). Interestingly, the IFN-gamma mRNA copies in cultured lymphocytes correlated significantly with the intensity of lymphocytic infiltration as evaluated by Chisholm's score (P < 0.01). Furthermore, RT-PCR of RNA extracted from whole LSG from 14 SS patients also demonstrated the presence of all cytokines in the majority of the cases and the prevalence of IFN-gamma in LSG with high-grade infiltration. Because IL-13 was produced by the majority of the cultured LSG, IgE production was also evaluated. Interestingly, IgE was detected in 21/44 LSG culture SN and mainly in those biopsies that had Chisholm's score less than 0.5 (P < 0.05). We conclude that lymphocytes infiltrating the LSG are capable of producing both Th1 and Th2 cytokines and that the balance between them shifts in favour of Th1 in LSG with high infiltration score and in patients with SS.     

Overexpression of interleukin-12 and T helper 1 predominance in lupus nephritis

Imbalance of cytokine homeostasis is a prominent feature of both experimental and human systemic lupus erythematosus (SLE). Because interleukin (IL)-12 promotes interferon (IFN)-gamma production leading to polarization of peripheral cells toward a T helper (Th) 1 phenotype, we investigated its role in lupus nephritis (LN). Soluble Th1 and Th2 cytokines were measured by enzyme-linked immunosorbent assay (ELISA) in sera and urines of SLE patients and controls. Th1/Th2 peripheral lymphocyte polarization was determined by flow cytometry. Glomerular accumulation of IL-12 was evaluated by immunohistochemistry, whereas urinary IL-12 was evaluated by ELISA. Higher serum IL-12 levels in SLE were associated with LN, whereas IL-4 was unrelated to the renal damage. Peripheral cells from LN patients showed a Th1 phenotype with a high IFN-gamma expression that paralleled the severity of renal damage. IL-12 was present within glomerular mononuclear cells in classes IV and V LN, and its accumulation was correlated strongly with urinary levels. IL-12 overexpression in SLE may contribute to the development of LN. Both serum and urinary IL-12 elevation reflect its glomerular production and parallel Th1 polarization of peripheral T cells and high IFN-gamma production. In SLE patients, IL-12 measurement may thus be predictive of the development of LN.     

Th1, Th2, and Th3 cytokine alterations in major depression

BACKGROUND: Many studies have shown that the balance between Th1 cytokines and Th2 cytokines plays a role in modulation of cellular responses in the brain during psychological stress and psychiatric disorders. The Th3 cytokine, transforming growth factor beta-1 (TGF-beta1), has been shown to regulate the balance between Th-1 and Th-2 cytokines. However, the role of TGF-beta1 in the psychoimmunology of depression has never been explored. METHODS: A total of 40 depressed patients and 80 normal controls were recruited. The plasma levels of IFN-gamma, IL-4, and TGF-beta1 were studied at the time of admission and 8 weeks after antidepressant treatment. RESULTS: The proportion of patients who showed immunoreactivity to IFN-gamma and IL-4 in the plasma, and the plasma IFN-gamma/IL-4 ratio, were significantly higher in depressed patients than in controls. The IFN-gamma/TGF-beta1 ratio was also higher in depressed patients, and TGF-beta1 levels showed a significant negative correlation with the HDRS depression scale. After treatment, TGF-beta1 level increased significantly, and the IFN-gamma/IL-4 ratio decreased significantly, in the patient group. However, Th1 changes in male and female showed different trend such as Th1 arm was decreased after the treatment in all male, whereas it was increased in premenopausal age women. LIMITATIONS: Replication and extension using a larger sample size are required. CONCLUSIONS: The Th1 and Th2 cytokine imbalance was observed in subpopulation of depressed patients. TGF-beta1 seemed to play a role in the pathophysiology of depression in this population. Moreover, antidepressant treatment was found to affect the Th1/Th2 balance through the action of TGF-beta1.     

SLE患者IFN-γ、IL-4及IL-12水平变化及意义

从Th1/Th2细胞代表性细胞因子IFN γ/IL 4和IL 12水平的变化分析SLE患者Th1/Th2细胞的偏移现象。本实验通过半定量PCR法和ELISA酶联免疫检测法检测上述三种细胞因子含量。实验结果显示 ,SLE患者IL 4/IFN γ基因水平比值为0 32 8,高于对照组 (0 0 7)。ELISA检测显示IL 12在SLE患者血清中为 (38 39± 15 1)pg/ml,低于对照组 (84 97± 13 7)pg/ml(P <0 0 5 )。结论 :SLE患者Th1/Th2细胞因子平衡失调 ,IL 4细胞因子基因水平增高 ,同时血清中IL 12水平降低。     

血清Th1/Th2细胞因子水平与慢性丙型肝炎临床及干扰素疗效关系的研究

目的 探讨血清Th1和Th2细胞因子水平与慢性丙型肝炎患者病情进展及干扰素疗效的关系.方法 血清细胞因子检测应用ELISA法,HCV基因分型应用直接测序法,HCVRNA载量采用荧光定量PCR法.结果 慢性丙型肝炎患者血清IL-2和TGF-β含量明显低于健康对照组,IL-5含量明显高于后者;血清IL-6含量与ALT水平呈正相关,与RNA载量呈负相关;HCV基因型1型患者IL-6含量明显高于2型,2a型IL-2含量低于2b型;随着感染时间的延长,血清IL-2呈下降趋势,IL-6呈升高趋势,而TGF-β则先升高之后逐渐下降.干扰素治疗应答组和无应答组治疗前血清细胞因子水平均差异无统计学意义,但应答组治疗结束时IFN-γ含量较治疗前明显升高.结论 慢性丙型肝炎患者存在Th1/Th2细胞因子失衡并与临床表现相关;治疗前血清Th1/Th2细胞因子水平不能对疗效进行预测,干扰素诱导的Th1细胞优势反应与持续应答有关.