Reduction of antigenicity and allergenicity of genetically modified egg white allergen,ovomucoid third domain

Ovomucoid (Gal d1) is a major allergen in hen egg white, consisting of three tandem domains. In this study, five genetically modified third domain (DIII) mutants, which were substituted single or double amino acids within its IgE and IgG epitopes were compared with those prepared and their antigenicity and allergenicity with native analogue using Western immunoblot and enzyme-linked immunosorbent assay. The replacement of phenylalanine at 37 (F37) position with methionine caused drastical loss of IgG and IgE binding activities of human sera derived from egg allergic patients as well as disruption of the alpha-helix structure which comprises a part of the IgG and IgE epitopes. Substituting glycine at 32 position in conjunction with F37 showed a synergistic effect of decreasing antigenicity. The present study indicated that glycine 32 and phenylalanine 37 have an important role on its antigenicity and allergenicity as well as structural integrity of ovomucoid DIII.     

A role for IL-10-mediated HLA-DR7-restricted T cell-dependent events in development of the modified Th2 response to cat allergen

Although high dose exposure to inhaled cat allergen (Fel d 1) can cause a form of tolerance (modified Th2 response), the T cell mechanism for this phenomenon has not been studied. T cell responses to Fel d 1 were characterized in both allergic (IgE(pos)) and modified Th2 (IgE(neg)IgG(pos)) responders as well as serum Ab-negative controls (IgE(neg)IgG(neg)). Fel d 1 stimulated high levels of IL-10 in PBMC cultures from all individuals, with evidence of Th2 and Th1 cytokine skewing in allergic and control subjects, respectively. Using overlapping peptides, epitopes at the N terminus of Fel d 1 chain 2 were shown to stimulate strong T cell proliferation and to preferentially induce IL-10 (peptide 2:1 (P2:1)) or IFN-gamma (P2:2) regardless of the allergic status of the donor. Injection of cat extract during conventional immunotherapy stimulated expansion of IL-10- and IFN-gamma-producing chain 2 epitope-specific T cells along with increased Fel d 1-specific serum IgG and IgG4 Ab. Six of 12 modified responders expressed the major HLA-DRB1 allele, *0701, and both P2:1 and P2:2 were predicted ligands for this allele. Cultures from DR7-positive modified responders produced the highest levels of IL-10 to P2:1 in addition to other major and minor epitopes within chains 1 and 2. In the presence of anti-IL-10 mAb, both T cell proliferation and IFN-gamma production were enhanced in a Fel d 1- and epitope-specific manner. We conclude that IL-10-producing T cells specific for chain 2 epitopes are relevant to tolerance induction, and that DR7-restricted recognition of these epitopes favors a modified Th2 response.     

乳杆菌对牛乳β-乳球蛋白致敏小鼠淋巴细胞分泌Th1/Th2型细胞因子和抗体的体外影响

为了分析乳杆菌对致敏小鼠脾淋巴细胞分泌Th1/Th2细胞因子及抗体的体外影响,用牛乳β-乳球蛋白腹腔注射BALB/c小鼠建立过敏症模型,造模成功后,分离致敏小鼠的脾淋巴细胞并与4种活/死乳杆菌(107 CFU/mL)体外共同孵育,ELISA法检测细胞上清液中细胞因子(IL-12、IFN-γ和IL-4)和抗体(总IgE、β-Lg特异性IgE和总IgG)含量。4种活/死乳杆菌均可体外调节致敏小鼠脾淋巴细胞分泌细胞因子和抗体的水平,特别是热致死的发酵乳杆菌和嗜酸乳杆菌可提高淋巴细胞IL-12和IFN-γ的分泌,抑制IL-4的分泌,使其IFN-γ/IL-4比值(代表Th1/Th2细胞平衡)高于活菌,与空白对照组比较差异显著(P<0.05)。同时,这两株热致死菌还可显著下调细胞上清液中总IgE、特异性IgE和总IgG抗体的浓度(P<0.05)。试验结果表明乳杆菌可提高牛乳β-乳球蛋白致敏小鼠脾淋巴细胞的IFN-γ/IL-4比值,进而纠正Th2占优势的Th1/Th2失衡,下调抗体分泌量,且具有菌株特异性。     

New Lactococcus strain with immunomodulatory activity: enhancement of Th1-type immune response

Few studies exist dealing with the probiotic activity of lactococci, which are commonly used as starter bacteria in the manufacture of many kinds of fermented dairy products. Fifteen strains of the genus Lactococcus were examined for their probiotic activities, such as immunomodulatory effects. Six strains induced the production of cytokines (IL-12, IL-6, and TNF-alpha) in macrophage-like cell line J774.1, and the highest induction was observed with Lactococcus lactis subsp. lactis G50. The cytokine induction in the J774.1 cell line was almost entirely sustained after heat-killing of the strain. Spleen cells from BALB/c mice fed G50 culture produced more IL-12 and IFN-gamma and slightly less IL-4 and IL-6 than the control (i.e., without strain G50), indicating that strain G50 can enhance Th1-type immune response in vivo. The effect of the oral administration of strain G50 on antibody response in mice was also investigated. Mice were immunized with ovomucoid (OVM), a potent egg allergen, and the antibody level in the serum was then determined. The total IgE antibody level in the group treated with strain G50 was significantly lower than that of the control. The response of OVM-specific IgG1 and IgE antibodies tended to be low in the group that was administered strain G50, compared with the response of the control group. These results suggest that strain G50 has an ability to suppress the Th2 response. Thus, Lactococcus lactis subsp. lactis G50 is a potential probiotic strain for the suppression of hypersensitive reactions caused by the Th2 response.     

Regulation of Exacerbated Immune Responses in Human Peripheral Blood Cells by Hydrolysed Egg White Proteins

The anti-allergic potential of egg white protein hydrolysates (from ovalbumin, lysozyme and ovomucoid) was evaluated as their ability to hinder cytokine and IgE production by Th2-skewed human peripheral blood mononuclear cells (PBMCs), as well as the release of pro-inflammatory factors and generation of reactive oxygen species from Th1-stimulated peripheral blood leukocytes (PBLs). The binding to IgE of egg allergic patients was determined and the peptides present in the hydrolysates were identified. The hydrolysates with alcalase down-regulated the production of Th2-biased cytokines and the secretion of IgE to the culture media of Th2-skewed PBMCs, and they significantly neutralized oxidative stress in PBLs. The hydrolysates of ovalbumin and ovomucoid with pepsin helped to re-establish the Th1/Th2 balance in Th2-biased PBMCs, while they also inhibited the release of pro-inflammatory mediators and reduced oxidative stress in PBLs treated with inflammatory stimuli. The hydrolysates with alcalase, in addition to equilibrating Th2 differentiation, exhibited a low IgE-binding. Therefore, they would elicit mild allergic reactions while retaining T cell-stimulating abilities, which might correlate with an anti-allergic benefit.     

应用体内外实验筛选可降低牛乳β-乳球蛋白过敏的乳杆菌

【目的】通过体内外实验评估5种乳杆菌缓解牛乳β-乳球蛋白(BLG)过敏的作用,为今后筛选具有抗过敏活性的乳杆菌提供参考。【方法】首先体外分析5种活的/热致死的乳杆菌促进小鼠原代淋巴细胞分泌细胞因子(CK)IFN-γ和IL-4的水平,随后应用小鼠BLG过敏模型评估这5种乳杆菌抑制过敏的能力。将实验动物随机分为空白组、BLG致敏组和5种活的/热致死乳杆菌组。采用ELISA法检测各组小鼠淋巴细胞分泌Thl/Th2型CK的水平,并测定小鼠血清中总IgE和BLG特异性IgE的含量。【结果】在体外可促进淋巴细胞分泌IFN-γ、抑制IL-4,使其IFN-γ/IL-4比值(代表Thl/Th2细胞平衡)显著高于正常对照组(P<0.05)的乳杆菌,在体内实验中也能有效提高致敏小鼠淋巴细胞的IFN-γ/IL-4分泌率,并显著降低致敏小鼠血清中总IgE和BLG特异性IgE的水平(P<0.05)。相反,在体外的IFN-γ/IL-4比值较低的乳杆菌,不能缓解特异性IgE抗体介导的食物过敏反应。【结论】基于乳杆菌体外刺激小鼠原代淋巴细胞分泌Th1/Th2型CK的结果,可以预测菌株在体内具有可通过纠正Th2占优势的Th1/Th2细胞失衡,下调抗体分泌量,缓解小鼠BLG过敏症状的能力。     

Genetic attachment of undecane peptides to ovomucoid third domain can suppress the production of specific IgG and IgE antibodies

An undecane peptide (Gly-Ser-Pro-Gly-Ile-Pro-Gly-Ser-Thr-Gly-Met) was genetically attached to the N-terminus of ovomucoid third domain (DIII) to investigate structural characteristics of linear IgE and IgG (B cell) epitopes in DIII with respect to modulation of the immune response towards antigenicity and allergenicity. Balb/c mice were sensitized with native DIII, wild type recombinant DIII, and recombinant modified DIII containing the extra amino acid stretch. The immune responses to the antigens were compared using enzyme-linked immunosorbent assay. Interestingly, specific IgE and IgG levels were suppressed when the modified DIII was used as antigen. This was further confirmed by synthesizing immunodominant IgE and IgG epitopes of DIII on cellulose acetate membrane (SPOTs) and probing them with antibodies raised against DIII antigens. Anti-recombinant wild type DIII anti-serum showed strong binding activities to immunodominant IgE and IgG epitopes, while anti-modified DIII serum did not show any significant binding to the IgE and IgG epitopes. Thus, it is clearly demonstrated that the amino acid stretch in DIII is masking the immune reactive epitope. Genetical attachment of peptides into DIII was found to be effective in reducing the production of specific IgE and IgG antibodies in mice.     

IL-10-induced anergy in peripheral T cell and reactivation by microenvironmental cytokines: two key steps in specific immunotherapy.

Specific immunotherapy (SIT) is widely used for treatment of allergic diseases and could potentially be applied in other immunological disorders. Induction of specific unresponsiveness (anergy) in peripheral T cells and recovery by cytokines from the tissue microenvironment represent two key steps in SIT with whole allergen or antigenic T cell peptides (PIT). The anergy is directed against the T cell epitopes of the respective antigen and characterized by suppressed proliferative and cytokine responses. It is initiated by autocrine action of IL-10, which is increasingly produced by the antigen-specific T cells. Later in therapy, B cells and monocytes also produce IL-10. The anergic T cells can be reactivated by different cytokines. Whereas IL-15 and IL-2 generate Th1 cytokine profile and an IgG4 antibody response, IL-4 reactivates a Th2 cytokine pattern and IgE antibodies. Increased IL-10 suppresses IgE and enhances IgG4 synthesis, resulting in a decreased antigen-specific IgE:IgG4 ratio, as observed normally in patients after SIT or PIT. The same state of anergy against the major bee venom allergen, phospholipase A2, can be observed in subjects naturally anergized after multiple bee stings. Together, these data demonstrate the pivotal role of autocrine IL-10 in induction of specific T cell anergy and the important participation of the cytokine microenvironment in SIT. Furthermore, knowledge of the mechanisms explaining reasons for success or failure of SIT may enable possible predictive measures of the treatment.     

Administration of pentoxifylline during allergen sensitization dissociates pulmonary allergic inflammation from airway hyperresponsiveness

Asthma, a chronic inflammatory disease characterized by intermittent, reversible airflow obstruction and airway hyperresponsiveness (AHR), is classically characterized by an excess of Th2 cytokines (IL-13, IL-4) and depletion of Th1 cytokines (IFN-gamma, IL-12). Recent studies indicating an important role for Th1 immunity in the development of AHR with allergic inflammation suggest that Th1/Th2 balance may be important in determining the association of AHR with allergic inflammation. We hypothesized that administration of pentoxifylline (PTX), a phosphodiesterase inhibitor known to inhibit Th1 cytokine production, during allergen (OVA) sensitization and challenge would lead to attenuation of AHR in a murine model of allergic pulmonary inflammation. We found that PTX treatment led to attenuation of AHR when administered at the time of allergen sensitization without affecting other hallmarks of pulmonary allergic inflammation. Attenuation of AHR with PTX treatment was found in the presence of elevated bronchoalveolar lavage fluid levels of the Th2 cytokine IL-13 and decreased levels of the Th1 cytokine IFN-gamma. PTX treatment during allergen sensitization leads to a divergence of AHR and pulmonary inflammation following allergen challenge.     

Critical role of preconceptional immunization for protective and nonpathological specific immunity in murine neonates

Expression of Th2 immunity against environmental Ags is the hallmark of the allergic phenotype and contrasts with the Th1-like pattern, which is stably expressed in healthy adults throughout life. Epidemiological studies indicate that the prenatal environment plays an important and decisive role in the development of allergy later in life. Since the underlying mechanisms were unclear, an animal model was developed to study the impact of maternal allergy on the development of an allergic immune response in early life. An allergic Th2 response was induced in pregnant mice by sensitization and aerosol allergen exposure. Both, IgG1 and IgG2a, but not IgE, Abs cross the placental barrier. Free allergen also crosses the placental area and was detected in serum and amniotic fluids of neonatal F(1) mice. These F(1) mice demonstrated a suppressed Th1 response, as reflected by lowered frequencies and reduced levels of IFN-gamma production. Development of an IgE response against the same allergen was completely prevented early in life. This effect was mediated by diaplacental transfer of allergen-specific IgG1 Abs. In contrast, allergic sensitization against a different allergen early in life was accelerated in these mice. This effect was mediated by maternal CD4 and OVA-specific Th2 cells induced by allergic sensitization during pregnancy. These data indicate a critical role for maternal T and B cell response in shaping pre- and postnatal maturation of specific immunity to allergens.     

Counterregulation of Th2 immunity by interleukin 12 reduces host defenses against Strongyloides venezuelensis infection

The aim of this study was to investigate the role of interleukin 12 (IL-12) during Strongyloides venezuelensis infection. IL-12^−/− and wild-type C57BL/6 mice were subcutaneously infected with 1500 larvae of S. venezuelensis. On days 7, 14, and 21 post-infection, we determined eosinophil and mononuclear cell numbers in the blood and broncoalveolar lavage fluid (BALF), Th2 cytokine secretion in the lung parenchyma, and serum antibody levels. The numbers of eggs in the feces and worm parasites in the duodena were also quantified. The eosinophil and mononuclear cell counts and the concentrations of IL-3, IL-5, IL-10, IL-13, and IgG1 and IgE antibodies increased significantly in infected IL-12^−/− and wild-type mice as compared with uninfected controls. However, the number of eosinophils and mononuclear cells in the blood and BALF and the Th2 cytokine levels in the lungs of infected IL-12^−/− mice were greater than in infected wild-type C57BL/6 mice. In addition, serum IgE and IgG1 levels were also significantly enhanced in the infected mice lacking IL-12. Meanwhile, parasite burden and fecal egg counts were significantly decreased in infected IL-12^−/− mice. Together, our results showed that the absence of IL-12 upregulates the Th2 immune response, which is important for control of S. venezuelensis infection.     

Inducing tolerance by intranasal administration of long peptides in naive and primed CBA/J mice

To assess the capacity of a peptide-based immunotherapy to induce systemic tolerance via the nasal route, we designed three long overlapping peptides of 44-60 aa covering the entire sequence of phospholipase A2 (PLA2), a major bee venom allergen. Both prophylactic and therapeutic intranasal administrations of long peptides to PLA2-hypersensitive CBA/J mice induced specific T cell tolerance to the native allergen. In prophylactic conditions, this tolerance was marked by a suppression of subsequent specific IgE response, whereas the therapeutic approach in presensitized mice induced a more than 60% decrease in PLA2-specific IgE. This decline was associated with a shift in the cytokine response toward a Th1 profile, as demonstrated by decreased PLA2-specific IgG1 and enhanced IgG2a levels, and by a decline in the specific IL-4/IFN-gamma ratios. T cell transfer from long peptide-tolerized mice to naive animals abrogated the expected anti-PLA2 IgE and IgG1 Ab response, as well as specific T cell proliferation, but enhanced specific IgG2a response upon sensitization with PLA2. These events were strongly suggestive of a clonal anergy affecting more profoundly Th2 than the Th1 subsets. In conclusion, these results demonstrate that allergen-derived long peptides delivered via the nasal mucosa may offer an alternative to immunotherapy with native allergens without the inherent risk of systemic anaphylactic reactions. Moreover, long peptides, in contrast to immunotherapy strategies based on short peptides, have the advantage of covering all potential T cell epitopes, and may represent novel and safe tools for the therapy of allergic diseases.     

Important roles of CD32 in promoting suppression of IL-4 induced immune responses by a novel anti-IL-4Rα therapeutic antibody

ABSTRACT

Asthma is characterized by airway hyperresponsiveness and inflammation, as well as underlying structural changes to the airways. Interleukin-4 (IL-4) is a key T-helper type 2 (Th2) cytokine that plays important roles in the pathogenesis of atopic and eosinophilic asthma. We developed a novel humanized anti-IL-4Rα antibody that can potently inhibit IL-4/IL-13-mediated TF-1 cell proliferation. Using monocytes isolated from human peripheral blood mononuclear cells (PBMCs), we revealed a critical role of CD32 in modulating the immune responses of monocytes in response to blockade of IL-4Rα signaling pathway. We, therefore, devised a new strategy to increase the efficacy of the anti-IL-4Rα monoclonal antibody for the treatment of asthma and other atopic diseases by co-engaging CD32 and IL-4Rα on monocytic cells by choosing IgG classes or Fc mutations with higher affinities for CD32. The antibody with selectively enhanced affinity for CD32A displayed superior suppression of IL-4-induced monocytes’ activities, including the down-regulation of CD23 expression. Intriguingly, further analysis demonstrated that both CD32A and CD32B contributed to the enhancement of antibody-mediated suppression of CD23 expression from monocytes in response to blockade of IL-4Rα signaling. Furthermore, inhibition of IgE secretion from human PBMC by the antibody variants further suggests that the complex allergic inflammation mediated by IL-4/IL-4Rα signaling might result from a global network where multiple cell types that express multiple FcγRs are all involved, of which CD32, especially CD32A, is a key mediator. In this respect, our study provides new insights into designing therapeutic antibodies for targeting Th2 cytokine-mediated allergic pathogenesis.     

Egg deposition is the major stimulus for the production of Th2 cytokines in murine schistosomiasis mansoni.

To characterize Th cell populations induced by helminth infection, spleen cells from mice infected with Schistosoma mansoni were stimulated with parasite (worm or egg Ag) or mitogen (Con A) and the supernatants assayed for the Th1-specific cytokines IFN-gamma and IL-2 and the Th2-specific cytokines IL-4 and IL-5. Th2 cytokine production was not detected in substantial quantity until the 6 to 8th wk of infection and after reaching peak levels at 8 to 12 wk declined slowly thereafter. The time courses of IL-4 and IL-5 production, whereas differing from each other, closely resembled corresponding published data on IgE and peripheral blood eosinophil levels during murine schistosome infection. In contrast, Th1 cytokine responses occurred only during the first 6 wk of infection and were virtually absent during the peak period of Th2 production. To assess the role of egg deposition in the observed pattern of Th response, cytokine production was assayed in mice carrying unisexual schistosome infections in which parasite eggs are absent. Splenocytes from these animals displayed only marginal Th2 cytokine synthesis but greater Th1 cytokine responses than the corresponding cells from mice with bisexual infections. Moreover, cultures of liver tissue or isolated granulomas from infected mice constitutively produced high levels of IL-4 and IL-5 but failed to synthesize significant amounts of IL-2 and IFN-gamma even when stimulated with egg Ag or mitogen. Taken together the data indicate that egg deposition is the major stimulus of Th2 cytokine response in S. mansoni-infected mice and suggest that T cells belonging to this subset must play a major role in egg granuloma formation.     

T regulatory cells 1 inhibit a Th2-specific response in vivo

We recently described a new population of CD4(+) regulatory T cells (Tr1) that inhibits proliferative responses of bystander T cells and prevents colitis induction in vivo through the secretion of IL-10. IL-10, which had been primarily described as a Th2-specific cytokine inhibiting Th1 responses, has displayed in several models a more general immune suppression on both types of effector T cell responses. Using an immediate hypersensitivity model in which BALB/c mice immunized with OVA (alum) normally generate Th2-dominated responses, we examined the ability of OVA-specific Tr1 T cell clones to inhibit OVA-specific cytokines and Ab responses. In contrast to Th2 or Th1 T cell clones, transfer of Tr1 T cell clones coincident with OVA immunization inhibited Ag-specific serum IgE responses, whereas IgG1 and IgG2a synthesis were not affected. This specific inhibition was mediated in part through IL-10 secretion as anti-IL-10 receptor Abs treatment reverted the inhibitory effect of Tr1 T cell clones. Although specifically targeted to IgE responses, Tr1 clones' inhibitory effects were more profound as they affected Ag-specific Th2 cell priming both in term of proliferative responses and cytokine secretion. These results suggest that regulatory T cells may play a fundamental role in maintaining the balance of the immune system to prevent allergic disorders.     

Acinetobacter baumannii infection inhibits airway eosinophilia and lung pathology in a mouse model of allergic asthma

Allergic asthma is a dysregulation of the immune system which leads to the development of Th2 responses to innocuous antigens (allergens). Some infections and microbial components can re-direct the immune response toward the Th1 response, or induce regulatory T cells to suppress the Th2 response, thereby inhibiting the development of allergic asthma. Since Acinetobacter baumannii infection can modulate lung cellular and cytokine responses, we studied the effect of A. baumannii in modulating airway eosinophilia in a mouse model of allergic asthma. Ovalbumin (OVA)-sensitized mice were treated with live A. baumannii or phosphate buffered saline (PBS), then intranasally challenged with OVA. Compared to PBS, A. baumannii treatment significantly reduced pulmonary Th2 cytokine and chemokine responses to OVA challenge. More importantly, the airway inflammation in A. baumannii-treated mice was strongly suppressed, as seen by the significant reduction of the proportion and the total number of eosinophils in the bronchoalveolar lavage fluid. In addition, A. baumannii-treated mice diminished lung mucus overproduction and pathology. However, A. baumannii treatment did not significantly alter systemic immune responses to OVA. Serum OVA-specific IgE, IgG1 and IgG2a levels were comparable between A. baumannii- and PBS-treated mice, and tracheobronchial lymph node cells from both treatment groups produced similar levels of Th1 and Th2 cytokines in response to in vitro OVA stimulation. Moreover, it appears that TLR-4 and IFN-γ were not directly involved in the A. baumannii-induced suppression of airway eosinophilia. Our results suggest that A. baumannii inhibits allergic airway inflammation by direct suppression of local pulmonary Th2 cytokine responses to the allergen.     

Silkworm dropping extract ameliorate trimellitic anhydride-induced allergic contact dermatitis by regulating Th1/Th2 immune response

Allergic contact dermatitis (ACD) is an inflammatory skin disease caused by hapten-specific immune response. Silkworm droppings are known to exert beneficial effects during the treatment of inflammatory diseases. Here, we studied whether topical treatment and oral administration of silkworm dropping extract (SDE) ameliorate trimellitic anhydride (TMA)-induced ACD. In ACD mice model, SDE treatment significantly suppressed the increase in both ear thickness and serum IgE levels. Furthermore, IL-1β and TNF-α levels were reduced by SDE. In allergic responses, SDE treatment significantly attenuated the production of the Th2-associated cytokine IL-4 in both ear tissue and draining lymph nodes. However, it increased the production of the Th1-mediated cytokine IL-12. Thus, these results showed that SDE attenuated TMA-induced ACD symptoms through regulation of Th1/Th2 immune response. Taken together, we suggest that SDE treatment might be a potential agent in the prevention or therapy of Th2-mediated inflammatory skin diseases such as ACD and atopic dermatitis.

Abbreviations: ACD: allergic contact dermatitis; AD: atopic dermatitis; APC: antigen presenting cells; CCL: chemokine (C-C motif) ligand; CCR: C-C chemokine receptor; Dex: dexamethasone; ELISA: enzyme-linked immunosorbent assay; IFN: interferon; Ig: immunoglobulin; IL: interleukin; OVA: ovalbumin; PS: prednisolone; SDE: silkworm dropping extract; Th: T helper; TMA: trimellitic anhydride; TNF: tumor necrosis factor     

Oral administration of ovalbumin after sensitization attenuates symptoms in a mouse model of food allergic enteropathy

Oral immunotherapy (OIT) is a promising treatment of food allergy. To administer an appropriate oral dose of an allergenic component as OIT to individuals sensitized with a food allergen may prevent inducing food allergic inflammation in them. So we attempted to establish a mouse model to evaluate efficacy for oral administration of food allergen after sensitization. In BALB/c mice sensitized by injecting ovalbumin (OVA) with alum twice, OVA was administered before inducing inflammation by feeding the mice with egg white (EW) diet. Severe inflammatory responses, such as enteropathy, weight loss, IL-4 production, and increase of IgE antibody levels, were suppressed by administration with 4 mg of OVA 7 times before feeding EW diet. OVA administration alone induced a slight Th2 response, but no symptoms. The current study demonstrated that severe food allergic enteropathy could be prevented by pre-administration with appropriate dose of OVA to sensitized mice.     

Cholesterol selectively enhances in vitro latex-specific IgE production in atopic dermatitis patients with latex allergy

Effect of cholesterol on in vitro latex-specific IgE production by mononuclear cells from atopic dermatitis patients with latex allergy. Cholesterol enhanced latex-specific IgE production in a dose-dependent fashion, and maximal enhancement was achieved at 1 microg/ml. In contrast, cholesterol had no effect on latex -specific IgA or IgG4 production. Study for cytokine production revealed that cholesterol decreased latex-induced production of IFN-gamma and IL-12, while it increased latex-induced production of IL-4, IL-10 and IL-13. These results indicate that cholesterol skews cytokine pattern toward Th2 type. Collectively, cholesterol may increase allergen-specific IgE production, which may in turn aggravate allergic symptoms.