scholarly journals Th2 Cytokine Levels Distort the Association of IL-10 and IFN-γ with Allergic Phenotypes

ISRN Allergy ◽  
2011 ◽  
Vol 2011 ◽  
pp. 1-6
Author(s):  
Guicheng Zhang ◽  
Catherine M. Hayden ◽  
Jack Goldblatt ◽  
Patrick Holt ◽  
Peter N. Le Souëf
Keyword(s):  
Total Serum ◽  
Staphylococcal Enterotoxin B ◽  
Th2 Cytokines ◽  
Th2 Cytokine ◽  
Regulatory Cytokine ◽  
Cytokine Levels ◽  
Dust Mite ◽  
Th1 Cytokine ◽  
Ifn Γ ◽  
Th1 Cytokines

The expression of allergic phenotypes involves complex inter-relationships among several Th2 and Th1 cytokines as well as the regulator cytokine interleukin (IL)-10. These direct or indirect interrelationships may distort the true associations of cytokine responses with these phenotypes. In this study, we aimed to clarify the effects of the regulatory cytokine IL-10 and Th1 cytokine interferon-gamma (IFN-γ) on allergic phenotypes after adjusting for the correlations with Th2 cytokines. After adjusting for Th2 cytokines, IL-10 and IFN-γ were protective against atopy. Adjusted levels of IL-10 and IFN-γ stimulated with house-dust mite (HDM) were significantly lower in atopics than non-atopics, for IL-10 adjusting for IL-5 (P=0.002), IL-13 (P=0.012), IL-9 (P=0.016), and IL-4 (P=0.043), and for IFN-γ adjusting for IL-5 (P=0.005), IL-13 (P=0.005), and IL-9 (P=0.037). IL-10 and IFN-γ levels stimulated with phytohaemagglutinin (PHA) and staphylococcal enterotoxin B (SEB) exhibited a similar pattern. The adjusted levels of IL-10 and IFN-γ stimulated with HDM, PHA or SEB were all significantly negatively correlated with total serum IgE, except for IFN-γ stimulated with SEB. Levels of Th2 cytokines distort the associations of IL-10 and IFN-γ with allergic phenotypes. Removing the covariance with Th2 cytokines, both IL-10 and IFN-γ were protective against atopy.

scholarly journals Cytokine Responses in Porcine Respiratory Coronavirus-Infected Pigs Treated with Corticosteroids as a Model for Severe Acute Respiratory Syndrome

2008 ◽  
Vol 82 (9) ◽  
pp. 4420-4428 ◽  
Author(s):  
Xinsheng Zhang ◽  
Konstantin Alekseev ◽  
Kwonil Jung ◽  
Anastasia Vlasova ◽  
Nagesh Hadya ◽  
...  
Keyword(s):  
Severe Acute Respiratory Syndrome ◽  
Glucocorticoid Treatment ◽  
Th2 Cytokine ◽  
Local Immunosuppression ◽  
Cytokine Levels ◽  
Th1 Cytokine ◽  
Th1 Cytokines ◽  
Respiratory Coronavirus ◽  
Phosphate Buffered Saline ◽  
Porcine Respiratory

ABSTRACT The effectiveness and potential immunosuppressive effects of anti-inflammatory glucocorticoids in the lungs of severe acute respiratory syndrome (SARS) patients are undefined. We treated porcine respiratory coronavirus (PRCV)-infected conventional pigs with the corticosteroid dexamethasone (DEX) as a model for SARS. Innate and Th1 cytokines in bronchoalveolar lavage (BAL) and serum were elevated in PRCV-infected pigs compared to controls, but were decreased after DEX treatment in the PRCV-infected, DEX-treated (PRCV/DEX) pigs. Although decreased in BAL, Th2 cytokine levels were higher in serum after DEX treatment. Levels of the proinflammatory cytokine interleukin-6 in BAL and serum were decreased in PRCV/DEX pigs early but increased later compared to those in phosphate-buffered saline-treated, PRCV-infected pigs, corresponding to a similar trend for lung lesions. PRCV infection increased T-cell frequencies in BAL, but DEX treatment of PRCV-infected pigs reduced frequencies of T cells; interestingly B and SWC3a+ (monocytes/macrophages/granulocytes) cell frequencies were increased. DEX reduced numbers of PRCV-stimulated Th1 gamma interferon-secreting cells in spleen, tracheobroncheolar lymph nodes, and blood. Our findings suggest that future glucocorticoid treatment of SARS patients should be reconsidered in the context of potential local immunosuppression of immune responses in lung and systemic Th1 cytokine-biased suppression.

scholarly journals Circulating Th1 and Th2 cytokines in patients with hepatitis C virus infection

1998 ◽  
Vol 7 (4) ◽  
pp. 295-297 ◽  
Author(s):  
X. G. Fan ◽  
W. E. Liu ◽  
C. Z. Li ◽  
Z. C. Wang ◽  
L. X. Luo ◽  
...  
Keyword(s):  
Hcv Infection ◽  
Th2 Cytokines ◽  
Th1 And Th2 Cytokines ◽  
Th1 Cytokine ◽  
Chronic Hcv Infection ◽  
Ifn Γ ◽  
Chronic Hcv ◽  
Th1 Cytokines ◽  
Normal Controls ◽  
Th1 And Th2

The imbalance of T-helper (Th) lymphocyte cytokine production may play an important role in immunopathogenes is of persistent hepatitis C virus (HCV) infection. To know whether an imbalance between Th1 and Th2 cytokines is present in chronic HCV infection, serum levels of Th1 cytokines , interferon gamma (IFN-γ ) and interleukin (IL)-2, and Th2 cytokines, IL-4 and IL-10, were measured using enzyme - linked immunosorbent as say in this study. Eighteen individuals with chronic HCV infection, 11 healthy subjects as normal controls and 10 chronic HBV infected patients as disease controls were observed. The results showed that the leve ls of Th2 cytokines (IL-4 and IL-10) were significantly increased inchronic HCV infected patients compared with normal controls (IL-4: 30.49 ± 17.55 vs . 14.94 ± 13.73, pg/ml,p<0.025; IL-10: 50.30 ± 19.59 vs. 17.87 ± 9.49, pg/ml,p<0.001). Similarly, the levels of Th1 cytokine, IL-2, was also elevated in individuals with chronic HCV infection when compared with normal controls (IL-2: 118.53 ± 95.23 vs . 61.57 ± 28.70, pg/ml,p<0.05). However, Th1 cytokine IFN-γ level was not significantly changed during HCV infection (IFN-γ: 28.09 ± 15.65 vs . 24.10 ± 15.61, pg/ml,p>0.05). Further more, the elevated levels of Th2 cytokines are greater than Th1 cytokines in HCV infection. Thus , the study indicates that an enhanced Th2 responses are present during chronic HCV infection, which may partly be responsible for the persistence of HCV infection.

Effect and Mechanism of Ligustrazine on Th1/Th2 Cytokines in a Rat Asthma Model

2007 ◽  
Vol 35 (06) ◽  
pp. 1011-1020 ◽  
Author(s):  
Liang Xiong ◽  
Zheng-Yu Fang ◽  
Xiao-Nan Tao ◽  
Ming Bai ◽  
Gang Feng
Keyword(s):  
Underlying Mechanism ◽  
Lavage Fluid ◽  
Enzyme Linked Immunosorbent Assay ◽  
Control Group ◽  
Th2 Cytokines ◽  
Asthma Model ◽  
Th2 Cytokine ◽  
Th1 Cytokine ◽  
Ifn Γ ◽  
Bet Protein

Ligustrazine is an alkaloid isolated from the rhizome of Chuanxiong (Ligusticum chuanxiong Hort), which is known to possess antioxidant, anti-inflammatory, anti-fibrosis and immunomodulative effects. It is used clinically to treat asthma as an assistant therapy of glucocorticoid. The purpose of this study was to explore the effects of intraperitoneal ligustrazine on Th1/Th2 cytokines in a rat asthma model and the underlying mechanism. SD rats were sensitized and challenged with ovalbumin (OVA) to establish an asthmatic model. Within 24 hours after the last ovalbumin challenge, changes in airway histology were observed. The concentrations of IL-4 and IFN-γ in bronchoalveolar lavage fluid (BALF) were measured by enzyme linked immunosorbent assay (ELISA). The protein expressions of GATA-3 and T-bet in lung were measured by Western blot. The results showed that an increase of Th2 cytokine and an inhibition of Th1 cytokine were accompanied by an increased expression of GATA-3 protein and a decreased expression of T-bet protein in rat asthmatic airways compared to those in normal control group. Intraperitoneal ligustrazine administration could significantly lower the level of IL-4 in BALF and the expression of GATA-3 protein in lung and also increase the level of IFN-γ and T-bet in asthmatic rats, resulting in a decreased percentage of eosinophils (EOS) in BALF and ameliorated airway inflammatory cell infiltration. In conclusion, ligustrazine inhibits OVA induced airway inflammation by modulating key master switches GATA-3 and T-bet that result in reversing the Th2 cytokine patterns in asthma.

Paracoccidioidomycosis: characterization of subpopulations of macrophages and cytokines in human mucosal lesions

2018 ◽  
Vol 57 (6) ◽  
pp. 757-763 ◽  
Author(s):  
C Pagliari ◽  
L Kanashiro-Galo ◽  
A C C Jesus ◽  
M G Saldanha ◽  
M N Sotto
Keyword(s):  
Th2 Cytokines ◽  
Arginase 1 ◽  
Immunohistochemistry Analysis ◽  
Tnf Α ◽  
Ifn Γ ◽  
Mucosal Lesions ◽  
Th1 Cytokines ◽  
Necrosis Factor ◽  
Number Of Cells

AbstractMucosal lesions of paracoccidioidomycosis (PCM) are frequently described and clinically important. Macrophages are classified as M1 or M2. M1 are proinflammatory and M2 are related to chronicity. Dectin-1 recognizes β-glucan and plays an important role against fungal cells. The objective was to verify the presence of M1, M2, and dectin-1 and a possible correlation with Th1/Th2 cytokines in mucosal PCM lesions. In sum, 33 biopsies of oral PCM were submitted to histological and immunohistochemistry analysis, and positive cells were quantified. Eleven biopsies were characterized by compact granulomas (G1), 12 with loose granulomas (G2), and 10 with both kind of granulomas (G3). pSTAT-1 was equally increased in the three groups. G1 was characterized by an increased number of CD163+ macrophages. G2 presented similar number of arginase 1, iNOS, and CD163 expressing cells. G3 presented an increased number of cells expressing arginase 1 and CD163 over iNOS. G1 and G3 presented high number of cells expressing interferon (IFN)-γ; interleukin (IL) 5 was increased in G2 and G3; the expression of IL10 was similar among the three groups, and the expression of tumor necrosis factor (TNF)-α was higher in G3. G1 correlates to Th1 cytokines and pSTAT-1 and G2 correlates to Th2 cytokines. G3 presents both kinds of cytokines. We could not associate the expression of arginase-1, CD163, iNOS, and dectin-1 with the pattern of cytokines or kind of granuloma.

scholarly journals Th2-driven, allergen-induced airway inflammation is reduced after treatment with anti–Tim-3 antibody in vivo

2007 ◽  
Vol 204 (6) ◽  
pp. 1289-1294 ◽  
Author(s):  
Jennifer Kearley ◽  
Sarah J. McMillan ◽  
Clare M. Lloyd
Keyword(s):  
Pulmonary Inflammation ◽  
Allergen Challenge ◽  
Airway Hyperreactivity ◽  
Th2 Cells ◽  
Antibody Treatment ◽  
Th2 Response ◽  
Th2 Cytokine ◽  
Cytokine Levels ◽  
Ifn Γ

T cell immunoglobulin and mucin domain–containing molecule-3 (Tim-3) is a surface molecule that is preferentially expressed on activated Th1 cells in comparison to Th2 cells. Blockade of Tim-3 has been shown to enhance Th1-driven pathology in vivo, suggesting that blockade of Tim-3 may improve the development of Th2-associated responses such as allergy. To examine the effects of Tim-3 blockade on the Th2 response in vivo, we administered anti–Tim-3 antibody during pulmonary inflammation induced by transfer of ovalbumin (OVA)-reactive Th2 cells, and subsequent aerosol challenge with OVA. In this model, anti–Tim-3 antibody treatment before each airway challenge significantly reduced airway hyperreactivity, with a concomitant decrease in eosinophils and Th2 cells in the lung. We examined Th1 and Th2 cytokine levels in the lung after allergen challenge and found that pulmonary expression of the Th2 cytokine IL-5 was significantly reduced, whereas IFN-γ levels were significantly increased by anti–Tim-3 antibody treatment. Thus, blocking Tim-3 function has a beneficial effect during pulmonary inflammation by skewing the Th2 response toward that of a Th1 type, suggesting an important role for Tim-3 in the regulation of allergic disease.

scholarly journals Th1/Th2 Cytokine Profile in Patients Coinfected with HIV and Leishmania in Brazil

2011 ◽  
Vol 18 (10) ◽  
pp. 1765-1769 ◽  
Author(s):  
Maria Zilma Andrade Rodrigues ◽  
Maria Fernanda Rios Grassi ◽  
Sanjay Mehta ◽  
Xing-Quan Zhang ◽  
Luana Leandro Gois ◽  
...  
Keyword(s):  
Immune Responses ◽  
Peripheral Blood Mononuclear Cells ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Peripheral Blood Mononuclear ◽  
Content Type ◽  
Th2 Cytokine ◽  
Cytokine Levels ◽  
Blood Mononuclear Cells ◽  
Ifn Γ

ABSTRACTTo evaluate the effects of HIV on immune responses in cutaneous leishmaniasis (CL), we quantified cytokine levels from plasma and stimulated peripheral blood mononuclear cells (PBMCs) from individuals infected with HIV and/or CL. Gamma interferon (IFN-γ) and interleukin 13 (IL-13) levels and the ratio of IFN-γ to IL-10 produced in response to stimulation with solubleLeishmaniaantigens were significantly lower in HIV-Leishmania-coinfected patients than in CL-monoinfected patients.

Cytokine Production and Proliferation in Mixed Lymphocyte Culture (MLC) May Predict Donor Engraftment in Adult Recipients of Multiple Umbilical Cord Blood (UCB) Unit Transplantation.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 1832-1832
Author(s):  
L. R. Fanning ◽  
M. Tary-Lehmann ◽  
J. Jaroscak ◽  
P. Rubinstein ◽  
T. McCormick ◽  
...  
Keyword(s):  
Cytokine Production ◽  
Mixed Lymphocyte Culture ◽  
Lymphocyte Culture ◽  
Hla Typing ◽  
Th2 Cytokines ◽  
Hla Antigen ◽  
Th1 Response ◽  
Cell Dose ◽  
Th1 Cytokine ◽  
Th1 Cytokines

Abstract Limited cell dose within a single UCB graft provides the rationale for multiple UCB unit transplantation. Our single institution phase I study testing the safety and efficacy of multiple UCB unit infusion targeted a nucleated cell dose of minimum ≥ 5x107cells/kg, and patients were transplanted with 3-5 unrelated UCB units. Seven adult patients (median 56 years; range 20–69) with advanced hematologic malignancies (4 AML, 1 ALL, 2 NHL) were enrolled and treated with non-myelablative conditioning including Fludarabine 150mg/m2, Cyclophosphamide 2gm/m2, and ATGAM 60mg/kg. UCB grafts were not T-depleted. All UCB units were 1-2 HLA antigen mismatched with the patient, and HLA matching between units was not required. The patients were transplanted sequentially and received a median infused total nucleated cell dose: 5.4x107/kg (range 4.2–8.9), CD3+: 1.4x107/kg (range 1.4–3.4), and CD34+: 2.2x105/kg (range 1.9–5.3). Three of the 7 patients demonstrated UCB donor engraftment while 3 patients had autologous recovery, and one patient died prior to engraftment (day=56). Mixed lymphocyte culture (MLC) was performed including proliferation and cytokine production in order to evaluate impact of graft-graft and patient-graft immune reactivity on donor engraftment. Cryogenically preserved pre-transplant patient and corresponding UCB graft samples were thawed for MLC with readouts including proliferation (CFSE staining) and cytokine production (cytometric bead assay-CBA)(Becton Dickinson, Franklin Lakes, NJ) including pro-inflammatory TH1 cytokines (IFN-γ, TNF-α, IL-2) and anti-inflammatory TH2 cytokines (IL-10, IL-5, IL-4). We hypothesize that increased proliferation and a strong TH1 response may be detrimental to engraftment which was confirmed by preliminary analysis (n=4). We observed higher rates of proliferation as well as higher TH1 cytokine production within the MLC of patients who did not attain donor engraftment. Table 1: TH1 Cytokine Output and Proliferation of Patient and Graft Mixed Lymphocyte Cultures Patient Number Number of UCB Units Donor Engraftment IFNγ(pg/mL) TNFα (pg/mL) IL-2(pg/mL) % Proliferation Pt #1 5 No 940 226 79 16 Pt #2 3 No 234 56 46 20 Pt #3 3 Yes 32 <20 <20 9 Pt #4 5 Yes <20 <20 <20 N/A TH1 cytokines produced in graft-graft MLCs were also elevated in the non-engrafting patients over those of the engrafting patients. The TH1 response of graft-graft interactions was lower than patient-graft interactions, indicating a bi-directional immune response. PHA positive controls indicate the decreased TH1 cytokine production seen in engrafted patients was not due to an inability to be activated. No trends were identified in the TH2 cytokines measured. These preliminary results suggest that graft-graft immune interactions as well as patient-graft interactions may determine overall donor engraftment. We plan to prospectively test this hypothesis in our ongoing clinical trial. MLCs with TH1 cytokine readouts that are patient and UCB unit specific may predict donor engraftment after multiple unit infusion and may be used as an adjunct to HLA typing.

scholarly journals Role of Th1 and Th2 Cytokines in Immune Response to Uncomplicated Plasmodium falciparum Malaria

2002 ◽  
Vol 9 (2) ◽  
pp. 348-351 ◽  
Author(s):  
Donato Torre ◽  
Filippo Speranza ◽  
Massimo Giola ◽  
Alberto Matteelli ◽  
Roberto Tambini ◽  
...  
Keyword(s):  
Immune Response ◽  
Plasmodium Falciparum ◽  
Interleukin 12 ◽  
Th2 Cytokines ◽  
Th1 And Th2 Cytokines ◽  
Ifn Γ ◽  
Anti Inflammatory ◽  
Th1 Cytokines ◽  
Th1 And Th2

ABSTRACT 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-γ), 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-γ, 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-γ (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-γ 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-γ 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-γ may play a role in limiting progression from uncomplicated malaria to severe and life-threatening complications.

Defective antifungal T-helper 1 (TH1) immunity in a murine model of allogeneic T-cell–depleted bone marrow transplantation and its restoration by treatment with TH2 cytokine antagonists

Blood ◽  
2001 ◽  
Vol 97 (5) ◽  
pp. 1483-1490 ◽  
Author(s):  
Antonella Mencacci ◽  
Katia Perruccio ◽  
Angela Bacci ◽  
Elio Cenci ◽  
Roberta Benedetti ◽  
...  
Keyword(s):  
Bone Marrow ◽  
T Cell ◽  
Fungal Infections ◽  
Th2 Cytokines ◽  
T Helper ◽  
T Helper 1 ◽  
Cytokine Antagonists ◽  
Th2 Cytokine ◽  
Donor Type ◽  
Th1 Cytokines

Patients undergoing full haplotype-mismatched hematopoietic transplantations may experience severe intractable invasive fungal infections. To verify whether an imbalanced production of T-helper 1 (TH1) and TH2 cytokines may be responsible for susceptibility to fungal infections, C3H/HeJ (H-2k) recipient mice were lethally irradiated, received transplantations with T-cell–depleted allogeneic bone marrow (BM) cells from mice ofH-2d haplotype, and were infected withCandida albicans. At different time-points after transplantation, mice were assessed for pattern of TH cytokine production and susceptibility to infection. The results show that a long-term, donor-type chimerism was achieved as early as 2 weeks after BM transplantation (BMT), at the time when high-level production of TH2 cytokines (interleukin-4 [IL-4] and IL-10) and impaired production of TH1 cytokines (interferon-γ [IFN-γ] and IL-12] were observed. At this time, mice were highly susceptible to both disseminated and mucosal infections, as indicated by decreased survival, uncontrolled fungal growth, and failure to develop protective TH1 immunity. However, a predominant production of TH1 cytokines was observed by week 5 after BMT, at the time when mice developed donor-type protective TH1 responses and were resistant to infections. Therapeutic ablation of IL-4 or IL-10 greatly increased resistance to candidiasis. These results indicate that a dysregulated production of TH cytokines occurs in mice undergoing T-cell–depleted allogeneic BMT. The transient predominant production of TH2 cytokines over that of IL-12 impaired the ability of mice to develop antifungal TH1 resistance, an activity that could be efficiently restored upon treatment with TH2 cytokine antagonists.

scholarly journals Th1 Polarization of Cytokine and Cytokine Receptor Polymorphisms Affect the Susceptibility and Severity of ITP

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 2245-2245
Author(s):  
Noriyuki Takahashi ◽  
Takayuki Saitoh ◽  
Nanami Gotoh ◽  
Kei Kimura ◽  
Yuko Kuroda ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
Steroid Treatment ◽  
Cytokine Receptor ◽  
Function Type ◽  
Chronic Itp ◽  
Th2 Cytokine ◽  
Th1 Cytokine ◽  
Ifn Γ ◽  
Th1 Polarization ◽  
Low Expression

Abstract Introduction: Immune thrombocytopenia (ITP) is an acquired autoimmune disorder characterized by the production of platelet antibodies, resulting in the destruction of platelets and inhibition of their production. Many cytokine profile study have revealed a clear T helper type1 (Th1) cytokine polarization in chronic ITP patients, using quantitative RT-PCR and flow cytometry method. However, it remains unclear whether genetic factors of Th1/Th2 cytokine and cytokine receptor affect chronic ITP. We investigated the impact of IFN-γ+874T/A, IFN-γ receptor (R) -611G/A, IL-4 -590C/T, and IL-4 receptor (R) a Q576R polymorphisms on the susceptibility and clinical feature of chronic ITP and Th1/Th2 ratio in peripheral blood of ITP patients, Patients and methods: Genotyping was determined by PCR based technique and direct sequencing. The diagnosis and response criteria of the ITP were defined according to International Working Group criteria. We evaluated Th1/Th2 ratio in peripheral blood of 15 normal donors and 25 ITP patients by intracellular flow cytometry. Intracellular IL-4 (Th2 cytokine) and IFN-γ (Th1 cytokine) production was assessed in CD4+ T lymphocytes activated by phorbol 12-myristate 13-acetate and ionomycin by flow cytometry. This study was approved by the IRB of our hospital. Results: The platelet count ranged from 1´109/L to 98´109/L with a mean count of 32´109/L at the initial diagnosis. Eighty-three patients (56.1%) had bleeding tendency and 24 patients (16.2%) had severe thrombocytopenia (< 10 ´109/L). Steroid treatment was given to 86 patients (58.1%), and eradication of Helicobacter pylori was performed in 38 patients (25.7%), while splenectomy was performed in only 18 patients (12.2%). As compared to control group, chronic ITP patients had significantly higher frequency of the IL-4R576 non-QQ (low function type) than QQ (high function type) (29.7% vs 15.2%, P<0.05). ITP patients with IL-4-590 CC genotype (low expression type) showed lower platelet counts than those with IL-4-590 non-CC genotype (high expression type) (21±17 X109/mL vs 33±27 X109/mL, p<0.05). ITP patients with IFN-γ+874 non-AA genotype (high expression type) showed lower response rate to steroid treatment than those with IFN-γ+874 AA genotype (low expression type) (76.9% vs 97.5%, p<0.05). We examined the association between Th1/Th2 polymorphisms and Th1/Th2 ratio in both normal donors and ITP patients. Th1/Th2 ratio was not significantly different among IFN-γ+874T/A, IFN-γR-611G/A, IL-4-590C/T, and IL-4Ra Q576R polymorphisms in normal donors. In contrast, ITP patients with IL-4Ra576 non-QQ genotype (low function type) had higher tendency of Th1/Th2 ratio compared to IL-4Ra576 QQ genotype (high function type) (111.2±216.1 vs. 20.8±21.6, p = 0.12). Conclusion: These findings suggested that Th1 polarization of Th1/Th2 cytokine and cytokine receptor polymorphisms affect the susceptibility and severity of chronic ITP. Especially, IL-4Ra576 QQ genotype may be closely associated with the risk of ITP and Th1 polarization. Disclosures No relevant conflicts of interest to declare.

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