Asthma is a chronic allergic inflammatory disease of lung. The initiation and progression of asthma is dependent on the cytokines interleukin (IL) -4 and IL-13 acting through related receptor complexes. Disease pathogenesis is effected by intracellular signaling pathways that couple primarily to specific motifs within the intracellular domain of the IL-4 receptor alpha chain (IL-4R alpha), a subunit that is common to the IL-4 and IL-13 receptor complexes. Neutralizing anti-cytokine strategies have proven to be highly successful on dissecting relevant effector pathways in experimental allergic disease, and are now entering clinical trials in human allergic disorders. Although there have been only a few clinical studies on the effects of cytokine modulators in asthma, this line of research and development appears promising.
Asthma* ; Cytokines ; Humans ; Interleukin-13 ; Interleukin-4 ; Interleukins ; Lung ; Receptors, Interleukin-13 ; Receptors, Interleukin-4

T helper-type 2 cytokines, such as IL-4 and IL-13, may play a central role in allergic diseases. The protein known as signal transducers and activators of transcription 6 (STAT6) is a key transcription factor involved in both IL-4- and -13-mediated biological responses. Two polymorphisms of the STAT 6 gene (exon 1 and G2964A variant) have been found. We investigated whether these STAT6 gene polymorphisms were associated with allergic rhinitis. Blood samples for genetic analysis were obtained from 285 individuals with allergic rhinitis and from 271 healthy subjects without atopic disease. The G2964A variant of the STAT6 gene was genotyped using PCR-RFLP analysis. The GT repeat polymorphism in exon 1 of the STAT6 gene was genotyped by fragment analysis. There was no association between the 2964A variant and GT repeat polymorphism in exon 1 of the STAT6 and allergic rhinitis in a Korean population (both p > 0.05). Our results suggest that a combination of STAT6 gene polymorphisms is not a useful marker for predicting allergic rhinitis.
Cytokines ; Exons ; Interleukin-13 ; Interleukin-4 ; Rhinitis* ; Transcription Factors ; Transducers

BACKGROUND: A small subgroup of atopic dermatitis (AD) patients show low total and allergen-specific immunoglobulin (IgE) levels. This subgroup has been termed 'intrinsic' AD (IAD) as compared to its counterpart 'extrinsic' AD (EAD). However, the difference of cytokine expression between IAD and EAD has not been fully understood. OBJECTIVE: To compare the expression of various inflammatory cytokines in the peripheral blood mononuclear cells (PBMCs) and lesional skin of patients with IAD and EAD, which are known to be associated with AD pathophysiology. METHODS: We assessed the protein levels of cytokines in the PBMCs and lesional skin. We evaluated the levels of IL-3, IL-4, IL-5, IL-6, IL-10, IL-13, FcepsilonRI and FcepsilonRII from the PBMCs and lesional skin of patients with IAD and EAD. RESULTS: The patients with EAD had elevated levels of the IL-3 expression in their PBMCs and elevated levels of FcepsilonRI in their lesional skin compared to that of the patients with IAD. The expression of other cytokines did not differ in the PBMCs and lesional skin from the two subgroups. CONCLUSION: This study suggests that IL-3 could be associated with the pathophysiology of EAD as compared to that of IAD, along with FcepsilonRI which was previously shown to be highly expressed in EAD patients.
Cytokines ; Dermatitis, Atopic ; Humans ; Immunoglobulins ; Interleukin-10 ; Interleukin-13 ; Interleukin-3 ; Interleukin-4 ; Interleukin-5 ; Interleukin-6 ; Skin

Chronic spontaneous urticaria (CSU) is a complex idiopathic disease of the skin with various cellular infiltrations. Although mast cells are key effector cells in the pathogenesis of CSU, CD4+ T helper 2 cells also have particular roles in the development and maintenance of CSU. Periostin is known as a downstream molecule of interleukin (IL)-4 and IL-13, key cytokines of type 2 immune responses. In this study, we examined periostin and IL-13 levels in the sera of patients with CSU (n=84) and healthy normal controls (NCs, n=43). Periostin levels were significantly lower in the CSU group than in NCs (71.4±21.8 vs 85.1±22.4 ng/mL, P=0.04). Periostin levels were also lower in the severe CSU group than those in mild CSU (59.7±18.0 vs 73.4±22.0 ng/mL, P=0.04). However, IL-13 levels were significantly higher in patients with CSU than in NCs (508.5±51.2 vs 200.7±13.3 pg/mL, P=0.001). In conclusion, periostin and IL-13 may be independently related to the pathogenesis of CSU.
Cytokines ; Humans ; Interleukin-13* ; Interleukins ; Mast Cells ; Skin ; Urticaria*

BACKGROUND: It is well known that the expression of Th2 cytokines are up-regulated in the atopic asthma. The study was to investigate the expression of transcription factors, such as GATA-3, c-maf, T-bet which are known to be involved in the T cell differentiation in the peripheral blood mononuclear cells (PBMCs) of atopic asthmatics. METHODS: PBMCs were obtained from non-atopic controls and atopic asthmatics and cultured for 48 hours, and then 12-o-tetracanoylphorbol-13-acetate (PMA) and calcium ionophore (ionomycin) were added. mRNA of GATA-3, c-maf, T-bet, IL-4, IL-5, IL-13 and IFN-gamma were measured by RT-PCR RESULTS: mRNAs of Th2 cytokines, such as IL-4, IL-5 and IL-13 were expressed higher in the atopic asthmatics, and that of Th1 cytokine, IFN-gamma was expressed higher in the non-atopic controls. GATA-3 and c-maf were expressed higher and T-bet was expressed lower in the atopic asthmatics. Expressions of GATA-3, c-maf and T-bet were not changed with the stimulation of PMA/Ionomycin. CONCLUSION: This study suggest that GATA-3, c-maf and T-bet participate in the Th2 type inflammation in atopic asthmatics, like GATA-3 and c-maf as stimulatory factors, and T-bet as inhibitory factor.
Asthma ; Calcium ; Cell Differentiation ; Cytokines ; Inflammation ; Interleukin-13 ; Interleukin-4 ; Interleukin-5 ; RNA, Messenger* ; Transcription Factors

PURPOSE: Group 2 innate lymphoid cells (ILC2s) are a novel population of lineage-negative cells that induce innate type 2 responses by producing the critical Th2-type cytokines IL-5 and IL-13 in response to IL-25 and IL-33 stimulation. ILC2s accumulation in the peripheral blood of patients with allergic rhinitis (AR) is controversial; the precise role of ILC2s in the immunopathogenesis of AR is still not clear. We investigated the role of ILC2s in phenotypic AR sensitized to distinct allergens. METHODS: Flow cytometric analysis of the peripheral blood of 7 healthy controls (HCs), 9 patients monosensitized to house dust mite (HDM), and 8 patients monosensitized to mugwort was performed to quantify ILC2s frequency. Peripheral blood mononuclear cells (PBMCs) were isolated from HDM-AR and mugwort-AR patients, and Lineage- and Lineage+ cells were separated using a fluorescence-activated cell sorter (FACS). IL-5 and IL-13 levels in the supernatants of PBMCs, and Lineage- and Lineage+ cells stimulated with IL-25 and/or IL-33 combined with IL-2 in vitro were assessed using the Milliplex magnetic bead kit. RESULTS: The percentage of ILC2s was significantly elevated in HDM-AR patients compared to mugwort-AR patients and HCs, while no significant difference was found between mugwort-AR patients and HCs. IL-33+/-IL-25 plus IL-2 induced a significantly greater release of IL-5 and IL-13 in the PBMCs of HDM-AR patients compared to PBMCs of mugwort-AR patients. IL-25 plus IL-2 also induced a significantly greater release of IL-13 in the PBMCs of HDM-AR patients compared to PBMCs of mugwort-AR patients. Stimulation with IL-33 and/or IL-25 combined with IL-2 also induced a significantly greater IL-5 and IL-13 release from Lineage- cells compared to Lineage+ cells. CONCLUSIONS: AR patients sensitized to HDM or mugwort allergen have distinct phenotypic and functional profiles in ILC2s frequencies. ILC2s mediate major type 2 immunity in the development of HDM-AR and may be a potential therapeutic target.
Allergens ; Artemisia ; Cytokines ; Humans ; Interleukin-13 ; Interleukin-2 ; Interleukin-5 ; Lymphocytes ; Pyroglyphidae ; Rhinitis*

PURPOSE: Allergen-specific immunotherapy (IT) has been shown to be effective in the treatment for allergic diseases. But the immunologic mechanism of IT effect has not been fully elucidated. We studied house dust mite (HDM)-specific cytokine mRNA expression in peripheral blood mononuclear cells (PBMC) from patient with HDM- sensitive asthma and determined whether alterations in cytokine mRNA expression correlated with the clinical outcome of IT. METHODS: PBMC were obtained from 64 children with mite-sensitive asthma : 25 had never received HDM-IT (NIT), 39 had been receiving HDM-IT for more than 12 months. The 39 patients were divided into two groups according to the clinical response based on the asthma scores (symptom and medication scores) before and after IT. Good responders were those patients who showed an improvement greater than 50%, whereas poor responders were those who showed an improvement less than 50%. After a 18 hr culture with HDM, cytokine mRNA expression was analysed by RT-PCR and densitometry. RESULTS: 1) IL-10 mRNA expression in NIT was significantly lower than that in the normal controls and was significantly increased by IT. IL-10 mRNA expression in the good responders was significantly higher than that in the poor responders and NIT. 2) Little or no IL-13 mRNA were detected in the good responders and the normal controls. IL-13 mRNA expression in the good responders was significantly lower than that in the poor responders and NIT. 3) IFN-gamma mRNA expression in NIT was significantly lower than that in the normal controls and was significantly increased with IT. IFN-gamma mRNA expression in the good responders was significantly higher than that in the poor responders and NIT. 4) Little IL-4 mRNA were detected in the good responders and the normal controls. IL-4 mRNA expression in the good responders was significantly lower than that in the poor responders and NIT. CONCLUSION: These results show that IT not only induces a shift in cytokine expression from TH2 (IL-4 and IL-13) to TH1 cytokines (IFN-gamma), but also leads to induction of the antiinflammatory cytokine IL-10. These changes in cytokine expression may be responsible for clinical effects by immunotherapy.
Asthma* ; Child ; Cytokines ; Densitometry ; Humans ; Immunotherapy* ; Interleukin-10* ; Interleukin-13* ; Interleukin-4 ; Pyroglyphidae ; RNA, Messenger*

Idiopathic interstitial pneumonia (IIP) is characterized by varying degrees of interstitial fibrosis. IL-13 and IL-4 are strong inducers of tissue fibrosis, whereas IFN-gamma has antifibrotic potential. However, the roles of these substances in IIP remain unknown. IL-13, IL-4, and IFN-gamma were measured in the BAL fluid of 16 idiopathic pulmonary fibrosis (IPF) patients, 10 nonspecific interstitial pneumonia (NSIP) patients, and 8 normal controls. The expression of IL-13 and IL-13Ralpha1/alpha2 in lung tissues was analyzed using ELISA and immunohistochemistry. IL-13 levels were significantly higher in IPF patients than the others (P<0.05). IL-4 levels were higher in both IPF and NSIP patients than in normal controls (P<0.05), and IFN-gamma levels were lower in NSIP patients than in normal controls (P=0.047). IL-13 levels correlated inversely with FVC% (r=-0.47, P=0.043) and DLCO% (r=-0.58, P=0.014) in IPF and NSIP patients. IL-13 was strongly expressed in the smooth muscle, bronchial epithelium, alveolar macrophages and endothelium of IPF patients. IL-13Ralpha1, rather than IL-13Ralpha2, was strongly expressed in the smooth muscle, bronchial epithelium, and endothelium of IPF patients. IL-13 and its receptors may contribute to the pathogenesis of fibrosis in IIP and appear to be related to the severity of the disease.
Adult ; Female ; Humans ; Idiopathic Interstitial Pneumonias/diagnosis/*metabolism ; Idiopathic Pulmonary Fibrosis/diagnosis/*metabolism ; Interferon-gamma/analysis ; Interleukin-13/*analysis ; Interleukin-13 Receptor alpha1 Subunit/*metabolism ; Interleukin-13 Receptor alpha2 Subunit/*metabolism ; Interleukin-4/analysis ; Lung/physiopathology ; Male ; Middle Aged

Minmal change nephrotic syndrome(MCNS) has been often associated with elevated IgE levels and referred to involve immune dysfunction. We have reported that MCNS may be a T-cell disorder involving abnormal production of interleukin-4 and that the counter regulation of CD23 by Interleukin-4 may play a role in the pathogenesis of MCNS, however IgE is also regulated by Interleukin-13. In order to evaluate the role of IL-4 and IL-13 in the pathogenesis of MCNS, Ten(5 male, 5 female) patients with MCNS were studied along with 5 normal controls. Mean age was 7.9+/-4.53 years. In unstimulated MCNS samples, IL-4 levels were 2.71+/-0.61pg/mL (controls 0.90+/-0.00pg/mL) and IL-13 were 185.70+/-40.43pg/mL(controls 42.40+/-12.98pg/mL). In PHA-P stimulated samples, IL-4 were 6.25+/-1.90 pg/mL(controls 0.90+/-0.000) and IL-13 were 9,990.00+/-2,416.60 pg/mL(controls 2,020.00+/-176.49pg/mL). Although further studies are needed to confirm both IL-4 and IL-13 may be an important cytokines, however IL-4 might be more sensitive marker in the pathogenesis of MCNS.
Cytokines ; Humans ; Immunoglobulin E ; Interleukin-13* ; Interleukin-4* ; Male ; Nephrosis, Lipoid* ; T-Lymphocytes

Humans ; Interleukin-13 ; blood ; Interleukin-4 ; blood ; Rhinitis, Allergic, Perennial ; blood