Managing Food Allergies in Schools

Systemic contact dermatitis (SCD), a cutaneous reaction that is a direct manifestation of systemic exposure to a known allergen in a sensitized individual, has been increasingly recognized as a cause of persistent cutaneous contact dermatitis that is refractory to conventional therapies. While SCD in response to drugs has been described well in the literature, SCD to allergens in common foodstuffs is a less well-articulated phenomenon. Several foods that are universally consumed throughout the world contain potent allergens including nickel, balsam of Peru, trace metals, urushiol, and sesquiterpene lactones as well as a host of others that may cause a distinctive clinical picture. In this review article, the authors review the typical presentation and prevalence of SCD to foods, pathophysiology, the most common offensive ingestible food allergens, several appropriate diets, and effectiveness of dietary avoidance for situations in which SCD is suspected.     

Type 2 Innate Lymphocytes in Allergic Airway Inflammation

CD4⁺ T helper-2 (Th2) cells, which produce a unique profile of IL-4, IL-5 and IL-13 pro-inflammatory cytokines, are thought to be central in the orchestration and amplification of allergic asthma. However, a novel non-T/non-B lymphoid cell population, named type 2 innate lymphocytes (ILC2s), that produces high amounts of IL-5 and IL-13 was recently discovered. Unlike Th2 cells, these ILC2s are not antigen-restricted and are activated by epithelial cell-derived cytokines IL-25 and IL-33. In this review, we will focus on recent studies, mainly involving allergen-based mouse models, that have provided evidence for a significant contribution of ILC2 to allergic airway information.     

脑囊尾蚴病患者Th2型细胞因子的研究

目的 探讨脑囊尾蚴病患者Th2型细胞因子IL-4、IL-10、IL-13水平及其免疫调控作用。 方法 用淋巴细胞分离液密度梯度离心法分离淋巴细胞,按异硫氰酸胍一步法提取RNA,在逆转录酶作用下合成cDNA,用PCR法对cDNA进行扩增,最后对扩增产物进行电泳鉴定。 结果 30例脑囊尾蚴病患者外周血淋巴细胞,发现27例有细胞因子表达,3例未检测到细胞因子。在27例有细胞因子表达的患者中,IL-4、IL-10、IL-13的表达分别为16例、17例和14例,27例均有IL-4和(或)IL-10和(或)IL-13表达。10例健康人外周血淋巴细胞仅发现1例表达低水平的IL-4和IL-10,其余均未测出。 结论 脑囊尾蚴病患者Th2型细胞因子表达水平明显升高,其体液免疫功能增强。     

Pro-Inflammatory Cytokines in Omani Type 2 Diabetic Patients Presenting Anxiety and Depression

Background: The relationship of inflammatory cytokines with anxiety and depression has been reported, but their role in diabetic patients has not been fully elucidated. Objective: We examined whether an association between prevalence of anxiety and depression in Omani type-2 diabetic patients (n=30) and the levels of inflammatory markers such as IL-1β, TNF-α, IFN-γ and C-reactive protein (CRP) exists. Methods: Symptoms of anxiety and depression were screened using the Hospital Anxiety and Depression Scale (HADS) through self-rated questionnaires. IL-1β, TNF-α, IFN-γ, CRP, anti-TPO and anti-GAD65 antibodies were measured in patients' sera using commercially available ELISA assays. Results: In Omani type 2 diabetic patients, high prevalence of anxiety and depression along with high levels of inflammatory markers were detected. However, no correlation was observed between inflammatory markers and anxiety or depression. Conclusion: These results indicate that Omani type 2 diabetic patients are at great risk for developing anxiety and depression. Therefore, these complications need more care and attention. There was no association between scores of anxiety and depression with the levels of inflammatory cytokines. This may need to be elucidated in a larger cohort of patients.     

A Developmental,Community, and Psychosocial Approach to Food Allergies in Children

Recent estimates show that food allergies affect a substantial proportion of children in the United States and appear to have increased in prevalence. At present, management of food allergies consists of strict avoidance of the responsible allergen and an appropriate response should a reaction occur. Creating safe environments for the growing number of children with food allergies requires a partnership between affected families and members of the caregiving and educational communities. This article reviews issues affecting children with food allergies at different stages of psychosocial development and discusses strategies that can be implemented to promote food safety within child care and school environments as well as in the community. It also presents an overview of policy developments at the state and national level that have implications for children with food allergies.     

The Regulation of the IL-18 on Group 2 Innate Lymphoid Cells in Allergic Rhinitis

Background: Group 2 innate lymphoid cells (ILC2s) promote allergic inflammation by producing interleukin-4 (IL-4), IL-5, IL-9, and IL-13. IL-18 can promote T helper 2 cell (Th2) response by inducing IL-4, and IL-13 production from mast cells and basophils. However, the regulation of IL-18 on ILC2s remained unknown. Objective: To investigate the regulatory role of IL-18 in inducing the type 2 innate lymphoid cells. Methods: Twenty patients with allergic rhinitis (AR) and 20 controls were enrolled. The mRNA and protein levels of IL-18 in serum, as well as the frequencies of ILC2 in peripheral blood mononuclear cells (PBMCs) were measured by real-time polymerase chain reaction (PCR), enzyme-linked immunosorbent assay (ELISA), and flow cytometry. The ILC2s were sorted and the mRNA expression of IL-18 receptor in ILC2 was analyzed by real-time PCR. The effects of IL-18 on the proliferation and type 2 cytokine production were detected by tritiated thymidine incorporation test, real-time PCR, and ELISA, respectively. Results: The levels of IL-18 mRNA and protein were significantly higher in AR patients than in the controls (P<0.05). The frequency of ILC2 in peripheral blood was elevated in the AR patients than in the controls. After stimulation by IL-18 and house dust mite (HDM), the expression of IL-18 receptor (IL-18R) by ILC2 was significantly up-regulated. The tritiated thymidine incorporation results showed that IL-18 promoted the proliferation of ILC2 in a dose-dependent manner. IL-18 also induced the expression of IL-5 and IL-13 proteins by ILC2. Conclusion: Our results confirmed -for the first time- the effect of IL-18 in innate immunity, which was demonstrated by direct effect on the differentiation and function of ILC2.     

Aberrant Interaction of the Gut Immune System with Environmental Factors in the Development of Food Allergies

The gastrointestinal immune system is a major component of the mucosal barrier, which maintains an immunologic homeostasis between the host and the harsh environment of the gut. This homeostasis is achieved by immunologic quiescence, and its dysregulation is thought to result from the development of immune diseases such as food allergies. Recent findings have revealed versatile pathways in the development of intestinal allergies to certain food antigens. In this review, we summarize the regulatory and quiescence mechanisms in the gut immune system and describe aberrant interactions between the host immune system and the gut environment in the development of food allergies.     

Ethanol Feeding Impairs Innate Immunity and Alters the Expression of Th1- and Th2-Phenotype Cytokines in Murine Klebsiella Pneumonia

The prolonged and excessive consumption of alcohol has been shown to predispose the host to a variety of infectious complications, which may be due, in part, to the inability to produce important activating cytokines. In this study, we assessed the effect of chronic alcohol ingestion on bacterial clearance, survival, and cytokine mRNA and protein expression in mice with Klebsiella pneumonia. Two-week ethanol feeding resulted in substantial impairment in the clearance of K. pneumoniae and decreased survival, compared with CD-1 mice receiving an isocaloric diet without ethanol. No differences were noted between control and ethanol groups in the total numbers or percent of bronchoalveolar lavage fluid neutrophils or macrophages at 24 and 48 hr post-intratracheal K. pneumoniae. Importantly, the lungs of alcohol-fed mice with Klebsiella pneumonia displayed a decrease or delay in the expression of interleukin (IL)-12 p35 and p40 mRNA and interferon-γ mRNA, respectively, as well as reduced IL-12 and interferon-γ protein levels, compared with controls. Conversely, a time-dependent increase in lung IL-10 mRNA and protein was noted in ethanol-fed animals, compared with control animals challenged with K. pneumoniae. In summary, our studies indicate that ethanol ingestion results in a profound suppression of lung bacterial clearance and decreased survival in Klebsiella pneumonia, which occurs in association with a shift in the balance of lung cytokine mRNA and protein expression favoring Th2- rather than Th1-phenotype cytokines.     

C-Met Protooncogene Expression and Its Regulation by Cytokines in the Regenerating Pancreas and in Pancreatic Cancer Cells

Objective Jejunoileal (JI) bypass was a widely performed surgical procedure for morbid obesity in the 1970s. The purpose of this study was to assess cardiovascular risk factors and mortality in patients 25 years or more after this operation. Material and methods All (n=36) patients operated on for obesity with JI bypass at Haukeland University Hospital between 1971 and 1976 were evaluated. Survivors (n=28) participated in a follow-up that included clinical examination and biochemical tests. Preoperative data were compared with data at 1 year (3 years) and 25 years. Causes of death were identified for the deceased. Results For the 23 patients alive with intact JI shunts at 25 years there was a statistically significant lowering of body mass index (BMI) (p<0.01), systolic blood pressure (p<0.05), diastolic blood pressure (p<0.001) and serum cholesterol (p<0.05) compared to before the operation. There was no statistically significant change in fasting blood glucose or serum triglyceride. The serum insulin level was normal in all but one (21/22) of the patients examined. Three out of 26 patients with intact JI shunts, and 5 out of 10 patients with reversed JI shunts, had died. Conclusion For patients with intact shunts there is a persistent reduction in body weight, serum cholesterol and blood pressure, and a reduced insulin resistance 25 years after JI bypass.     

Promoting Immune Regulation in Type 1 Diabetes Using Low-Dose Interleukin-2

Dysregulation of the immune system contributes to the breakdown of immune regulation, leading to autoimmune diseases, such as type 1 diabetes (T1D). Current therapies for T1D include daily insulin, due to pancreatic β-cell destruction to maintain blood glucose levels, suppressive immunotherapy to decrease the symptoms associated with autoimmunity, and islet transplantation. Genetic risks for T1D have been linked to IL-2 and IL-2R signaling pathways that lead to the breakdown of self-tolerance mechanisms, primarily through altered regulatory T cell (Treg) function and homeostasis. In attempt to correct such deficits, therapeutic administration of IL-2 at low doses has gained attention due to the capacity to boost Tregs without the unwanted stimulation of effector T cells. Preclinical and clinical studies utilizing low-dose IL-2 have shown promising results to expand Tregs due to their high selective sensitivity to respond to IL-2. These results suggest that low-dose IL-2 therapy represents a new class of immunotherapy for T1D by promoting immune regulation rather than broadly suppressing unwanted and beneficial immune responses.     

Innate immunity defects in Hermansky-Pudlak type 2 syndrome

Adaptor protein-3 (AP-3) is an ubiquitous cytoplasmic complex that shuttles cargo proteins from the trans-Golgi and a tubular-endosomal compartment to endosome-lysosome-related organelles. Lack of the beta3A subunit of this complex causes Hermansky-Pudlak syndrome type 2, an autosomal recessive disease characterized by partial albinism, prolonged bleeding tendency, and immunodeficiency. To investigate the pathogenesis of immunodeficiency, we studied natural killer (NK) cells and neutrophil functions in 2 previously unreported siblings affected by Hermansky-Pudlak type 2 syndrome. In both patients we observed a dramatic reduction of cytolytic activity of freshly isolated and of IL-2-activated NK cells. Levels of perforin were reduced in unstimulated NK cells, thereby accounting for the impairment of NK cytolitic activity. In addition, analysis of neutrophils in these patients demonstrated that intracellular elastase content was largely reduced while CD63 expression on plasma membrane was substantially increased. Taken together, these observations suggest that type 2 Hermansky-Pudlak syndrome is characterized by defects of innate immunity.     

食物交换份法联合食物血糖生成指数指导2型糖尿病病人饮食治疗的临床观察

目的采用自身对照观察初发2型糖尿病病人单纯给予食物交换份法进行饮食治疗及其联合食物血糖生成指数（GI）进行饮食治疗前后病人血糖及胰岛素抵抗指数等指标的变化，评价两种饮食治疗方法的疗效。方法选择初发2型糖尿病病人18例，首先接受单纯食物交换份法治疗3个月，之后接受食物交换份法联合GI治疗3个月，比较饮食治疗前后及两种方法治疗后病人体重指数（BMI）、空腹血糖（FPG）和空腹胰岛素（FINs）、糖化血红蛋白（HbA1c）及胰岛素抵抗指数（HOMA-IR）的变化。结果单纯食物交换份法治疗3个月后，病人BMI、FPG、HbA1c、FINS及HOMA-IR较饮食治疗前均明显降低（P〈0．001或P〈0.01）。联合GI治疗3个月后，病人BMI、FPG、HbA1c及HOMA-IR较联合GI治疗前明显降低（P〈0.001或P〈0.01）；FINS有下降趋势，但无统计学意义（P〉0.05）。结论饮食治疗能够改善初发2型糖尿病病人的血糖及胰岛素敏感性，食物交换份法是一种有效的治疗方法，食物交换份法联合GI进行饮食治疗优于单纯食物交换份法。     

TRIMming Type I Interferon-Mediated Innate Immune Response in Antiviral and Antitumor Defense

The tripartite motif (TRIM) family comprises at least 80 members in humans, with most having ubiquitin or SUMO E3 ligase activity conferred by their N-terminal RING domain. TRIMs regulate a wide range of processes in ubiquitination- or sumoylation-dependent manners in most cases, and fewer as adaptors. Their roles in the regulation of viral infections, autophagy, cell cycle progression, DNA damage and other stress responses, and carcinogenesis are being increasingly appreciated, and their E3 ligase activities are attractive targets for developing specific immunotherapeutic strategies for immune diseases and cancers. Given their importance in antiviral immune response, viruses have evolved sophisticated immune escape strategies to subvert TRIM-mediated mechanisms. In this review, we focus on their regulation of IFN-I-mediated innate immune response, which plays key roles in antiviral and antitumor defense.     

Nature and Behavior of Serum Cytokines in Type 1 Autoimmune Hepatitis

To assess the relationship between serum cytokine behavior and treatment outcome in type 1 autoimmune hepatitis, serum levels of interferon-, interleukin-2, interleukin-4, and interleukin-10 were measured by enzyme immunoassay in 43 patients and 20 normal subjects. Serum samples were similarly tested in 38 patients after corticosteroid treatment. Serum levels of interleukin-2 and interleukin-4 were significantly lower in patients than in normal subjects. Interleukin-2 was the least common cytokine detected before (3%), during (0%), or after treatment (0%). Serum levels of interleukin-10 at presentation did not differ from those of normal subjects but they did decrease during therapy, especially in patients who entered remission. Changes in these levels, however, did not always parallel treatment outcome or histological activity. We conclude that serum levels of interleukin-2 and interleukin-4 are lower than normal in type 1 autoimmune hepatitis. Serum concentrations of interleukin-10 diminish during corticosteroid therapy but changes do not closely reflect outcome. The rarity of interleukin-2 in serum may be a distinguishing feature.