Concentrations of Cysteinyl Leukotrienes in Various Biological Fluids of Children with Bronchial Asthma, Atopic Dermatitis and Food Protein Induced Enterocolitis

Clinical manifestation of food allergy is characterized by polymorphic cutaneous, respiratory and gastrointestinal syndromes. Leukotrienes occupy a key place in the pathogenesis of a wide range of inflammatory diseases, including bronchial asthma, allergic rhinitis, atopic dermatitis, hives, allergic conjunctivitis, atherosclerotic cardio-vascular lesions system, inflammatory bowel disease, multiple sclerosis, cancer, etc. Better understanding of general pathophysiological mechanisms of allergic realization put the focus on the studying of cysteinyl leukotrienes biological effects in infants with atopic dermatitis and food-protein induced enterocolitis important.Aim. To optimize the diagnosis of allergic lesions of the gastrointestinal tract in children.Methods. The study was conducted in the allergy center and children clinic of the «Institute Pediatrics, Obstetrics and Gynecology named after academician O. Lukyanova of NAMS of Ukraine». Children were included from September 2017 to June 2018.We examined 60 patients aged from 3 months to 3 years old, including 22 patients with atopic dermatitis, 18 children with food-protein induced enterocolitis, 8 patients with bronchial asthma in the stage of aggravation and 12 practically healthy children (control group).Medical examination have been perfomed, general IG E and specific serum IG E were defined by ImmunoCAP (Phadia, 100), as well as concentrations of cysteinyl leukotrienes (LTB4, LTC4, LTE4) in biological liquids (serum, saliva, urine) using immunoenzyme method using the production sets of the "Enzolifescience" (USA) company on the analyzer-photometer Multiskan Plus "Labsystems". The results of the received data were processed statistically. The probability of differences was estimated with Student's t-test and Tau Kendall rank correlation test. The difference was considered significant at p <0.05.Results. A significant increase in the concentrations of cysteinyl leukotrienes (C4, D4, E4) in the blood, urine and saliva was found in infants with allergic skin diseases, gastro-intestinal and respiratory tract surveyed during manifestation the disease compared with the control group.Comparison of concentrations of leukotrienes in urine and saliva of children with atopic dermatitis (AD), food-protein induced enterocolitis (FPIE) and asthma did not find credible. However, in the serum of patients with asthma, the concentration of cysteinyl leukotrienes was significantly higher (703.9±68.7) pg / ml than in children with enterocolitis induced by dietary proteins (509.3±57.4) pg / ml and significantly did not differ from patients with atopic dermatitis (695.2±46.3) pg / ml.According to the results of Kendall Tau correlation test, no significant Spearman rank correlation was found between the cysteinyl leukotrienes concentration in blood and urine – r=0.14 (p>0.05), blood and saliva r=0.07 (p>0.05), urine and saliva r=–0.52 (p>0.05).Conclusions. Increase in cysteinyl leukotrienes concentrations in serum, urine and saliva of children of early age with allergic skin diseases, respiratory and gastrointestinal tract was found. The absence of significant Spearman rank correlation between concentrations of leukotrienes in blood and urine, blood and saliva, saliva and urine shows that it is possible to select any biological fluid, saliva or urine, as a non-invasive way to determine the leukotriene concentrations for monitoring activity of allergic inflammation

Concentrations of Cysteinyl Leukotrienes in Various Biological Fluids of Children with Bronchial Asthma, Atopic Dermatitis and Food Protein Induced Enterocolitis

Clinical manifestation of food allergy is characterized by polymorphic cutaneous, respiratory and gastrointestinal syndromes. Leukotrienes occupy a key place in the pathogenesis of a wide range of inflammatory diseases, including bronchial asthma, allergic rhinitis, atopic dermatitis, hives, allergic conjunctivitis, atherosclerotic cardio-vascular lesions system, inflammatory bowel disease, multiple sclerosis, cancer, etc. Better understanding of general pathophysiological mechanisms of allergic realization put the focus on the studying of cysteinyl leukotrienes biological effects in infants with atopic dermatitis and food-protein induced enterocolitis important.Aim. To optimize the diagnosis of allergic lesions of the gastrointestinal tract in children.Methods. The study was conducted in the allergy center and children clinic of the «Institute Pediatrics, Obstetrics and Gynecology named after academician O. Lukyanova of NAMS of Ukraine». Children were included from September 2017 to June 2018.We examined 60 patients aged from 3 months to 3 years old, including 22 patients with atopic dermatitis, 18 children with food-protein induced enterocolitis, 8 patients with bronchial asthma in the stage of aggravation and 12 practically healthy children (control group).Medical examination have been perfomed, general IG E and specific serum IG E were defined by ImmunoCAP (Phadia, 100), as well as concentrations of cysteinyl leukotrienes (LTB4, LTC4, LTE4) in biological liquids (serum, saliva, urine) using immunoenzyme method using the production sets of the "Enzolifescience" (USA) company on the analyzer-photometer Multiskan Plus "Labsystems". The results of the received data were processed statistically. The probability of differences was estimated with Student's t-test and Tau Kendall rank correlation test. The difference was considered significant at p <0.05.Results. A significant increase in the concentrations of cysteinyl leukotrienes (C4, D4, E4) in the blood, urine and saliva was found in infants with allergic skin diseases, gastro-intestinal and respiratory tract surveyed during manifestation the disease compared with the control group.Comparison of concentrations of leukotrienes in urine and saliva of children with atopic dermatitis (AD), food-protein induced enterocolitis (FPIE) and asthma did not find credible. However, in the serum of patients with asthma, the concentration of cysteinyl leukotrienes was significantly higher (703.9±68.7) pg / ml than in children with enterocolitis induced by dietary proteins (509.3±57.4) pg / ml and significantly did not differ from patients with atopic dermatitis (695.2±46.3) pg / ml.According to the results of Kendall Tau correlation test, no significant Spearman rank correlation was found between the cysteinyl leukotrienes concentration in blood and urine – r=0.14 (p>0.05), blood and saliva r=0.07 (p>0.05), urine and saliva r=–0.52 (p>0.05).Conclusions. Increase in cysteinyl leukotrienes concentrations in serum, urine and saliva of children of early age with allergic skin diseases, respiratory and gastrointestinal tract was found. The absence of significant Spearman rank correlation between concentrations of leukotrienes in blood and urine, blood and saliva, saliva and urine shows that it is possible to select any biological fluid, saliva or urine, as a non-invasive way to determine the leukotriene concentrations for monitoring activity of allergic inflammation

Update on Food protein-induced enterocolitis syndrome (FPIES)

Food protein-induced enterocolitis syndrome (FPIES) is a non-IgE mediated food allergy (FA) characterized by delayed and severe gastrointestinal symptoms that typically occurs within the first year of life. Many aspects of this pathology are currently unclear. FPIES is classified as a non-IgE immune-mediated FA in which the immune response is thought to act mainly through cell-mediated mechanisms. In patients with FPIES, the symptom pattern is determined by the frequency and dose of food allergen in the diet. Diagnosis of FPIES may be difficult, mainly due to the lack of specific biomarkers to confirm or exclude the diagnosis. FPIES is a clinical diagnosis, mainly based on clinical features which, although not specific, are reproducible every time the patient takes the food. Different diagnostic criteria of FPIES were published over time in the literature. The present narrative review aims to analyze the current clinical evidence in epidemiology, pathophysiology, diagnosis, and management of this condition

Vitamin C alleviates acute enterocolitis in Campylobacter jejuni infected mice

Human foodborne infections with the zoonotic pathogen Campylobacter jejuni are on the rise and constitute a significant socioeconomic burden worldwide. The health-beneficial, particularly anti-inflammatory effects of vitamin C (ascorbate) are well known. In our preclinical intervention study, we assessed potential anti-pathogenic and immunomodulatory effects of ascorbate in C. jejuni-infected secondary abiotic IL-10-/- mice developing acute campylobacteriosis similar to humans. Starting 4 days prior peroral C. jejuni-infection, mice received synthetic ascorbate via the drinking water until the end of the experiment. At day 6 post-infection, ascorbate-treated mice harbored slightly lower colonic pathogen loads and suffered from less severe C. jejuni-induced enterocolitis as compared to placebo control animals. Ascorbate treatment did not only alleviate macroscopic sequelae of infection, but also dampened apoptotic and inflammatory immune cell responses in the intestines that were accompanied by less pronounced pro-inflammatory cytokine secretion. Remarkably, the anti-inflammatory effects of ascorbate pretreatment in C. jejuni-infected mice were not restricted to the intestinal tract but could also be observed in extra-intestinal compartments including liver, kidneys and lungs. In conclusion, due to the potent anti-inflammatory effects observed in the clinical murine C. jejuni-infection model, ascorbate constitutes a promising novel option for prophylaxis and treatment of acute campylobacteriosis

A Multiorgan Trafficking Circuit Provides Purifying Selection of Listeria monocytogenes Virulence Genes.

Listeria monocytogenes can cause a life-threatening illness when the foodborne pathogen spreads beyond the intestinal tract to distant organs. Many aspects of the intestinal phase of L. monocytogenes pathogenesis remain unknown. Here, we present a foodborne infection model using C57BL/6 mice that have been pretreated with streptomycin. In this model, as few as 100 L. monocytogenes CFU were required to cause self-limiting enterocolitis, and systemic dissemination followed previously reported routes. Using this model, we report that listeriolysin O (LLO) and actin assembly-inducing protein (ActA), two critical virulence determinants, were necessary for intestinal pathology and systemic spread but were dispensable for intestinal growth. Sequence tag-based analysis of microbial populations (STAMP) was used to investigate the within-host population dynamics of wild-type and LLO-deficient strains. The wild-type bacterial population experienced severe bottlenecks over the course of infection, and by 5 days, the intestinal population was highly enriched for bacteria originating from the gallbladder. In contrast, LLO-deficient strains did not efficiently disseminate and gain access to the gallbladder, and the intestinal population remained diverse. These findings suggest that systemic spread and establishment of a bacterial reservoir in the gallbladder imparts an intraspecies advantage in intestinal occupancy. Since intestinal L. monocytogenes is ultimately released into the environment, within-host population bottlenecks may provide purifying selection of virulence genes.IMPORTANCE Listeria monocytogenes maintains capabilities for free-living growth in the environment and for intracellular replication in a wide range of hosts, including livestock and humans. Here, we characterized an enterocolitis model of foodborne L. monocytogenes infection. This work highlights a multiorgan trafficking circuit and reveals a fitness advantage for bacteria that successfully complete this cycle. Because virulence factors play critical roles in systemic dissemination and multiple bottlenecks occur as the bacterial population colonizes different tissue sites, this multiorgan trafficking circuit likely provides purifying selection of virulence genes. This study also serves as a foundation for future work using the L. monocytogenes-induced enterocolitis model to investigate the biology of L. monocytogenes in the intestinal environment

The role of mucosal immunity in the pathogenesis of necrotizing enterocolitis

Necrotizing enterocolitis (NEC) is the most devastating gastrointestinal disease of prematurity. Although the precise cause is not well understood, the main risk factors thought to contribute to NEC include prematurity, formula feeding, and bacterial colonization. Recent evidence suggests that NEC develops as a consequence of intestinal hyper-responsiveness to microbial ligands upon bacterial colonization in the preterm infant, initiating a cascade of aberrant signaling events, and a robust pro-inflammatory mucosal immune response. We now have a greater understanding of important mechanisms of disease pathogenesis, such as the role of cytokines, immunoglobulins, and immune cells in NEC. In this review, we will provide an overview of the mucosal immunity of the intestine and the relationship between components of the mucosal immune system involved in the pathogenesis of NEC, while highlighting recent advances in the field that have promise as potential therapeutic targets. First, we will describe the cellular components of the intestinal epithelium and mucosal immune system and their relationship to NEC. We will then discuss the relationship between the gut microbiota and cell signaling that underpins disease pathogenesis. We will conclude our discussion by highlighting notable therapeutic advancements in NEC that target the intestinal mucosal immunity

Carvacrol ameliorates acute campylobacteriosis in a clinical murine infection model

Background: The prevalence of human infections with the zoonotic pathogen Campylobacter jejuni is rising worldwide. Therefore, the identification of compounds with potent anti-pathogenic and anti-inflammatory properties for future therapeutic and/or preventive application to combat campylobacteriosis is of importance for global health. Results of recent studies suggested carvacrol (4-isopropyl-2-methylphenol) as potential candidate molecule for the treatment of campylobacteriosis in humans and for the prevention of Campylobacter colonization in farm animals. Results: To address this in a clinical murine infection model of acute campylobacteriosis, secondary abiotic IL-10-/- mice were subjected to synthetic carvacrol via the drinking water starting 4 days before peroral C. jejuni challenge. Whereas at day 6 post-infection placebo treated mice suffered from acute enterocolitis, mice from the carvacrol cohort not only harbored two log orders of magnitude lower pathogen loads in their intestines, but also displayed significantly reduced disease symptoms. Alleviated campylobacteriosis following carvacrol application was accompanied by less distinct intestinal apoptosis and pro-inflammatory immune responses as well as by higher numbers of proliferating colonic epithelial cells. Remarkably, the inflammation-ameliorating effects of carvacrol treatment were not restricted to the intestinal tract, but could also be observed in extra-intestinal organs such as liver, kidneys and lungs and, strikingly, systemically as indicated by lower IFN-γ, TNF, MCP-1 and IL-6 serum concentrations in carvacrol versus placebo treated mice. Furthermore, carvacrol treatment was associated with less frequent translocation of viable C. jejuni originating from the intestines to extra-intestinal compartments. Conclusion: The lowered C. jejuni loads and alleviated symptoms observed in the here applied clinical murine model for human campylobacteriosis highlight the application of carvacrol as a promising novel option for both, the treatment of campylobacteriosis and hence, for prevention of post-infectious sequelae in humans, and for the reduction of C. jejuni colonization in the intestines of vertebrate lifestock animals

Food protein induced enterocolitis syndrome caused by rice beverage

Food protein-induced enterocolitis syndrome (FPIES) is an uncommon and potentially severe non IgE-mediated gastrointestinal food allergy. It is usually caused by cow’s milk or soy proteins, but may also be triggered by ingestion of solid foods. The diagnosis is made on the basis of clinical history and symptoms. Management of acute phase requires fluid resuscitation and intravenous steroids administration, but avoidance of offending foods is the only effective therapeutic option. Infant with FPIES presented to our emergency department with vomiting, watery stools, hypothension and metabolic acidosis after ingestion of rice beverage. Intravenous fluids and steroids were administered with good clinical response. Subsequently, a double blind placebo control food challenge (DBPCFC) was performed using rice beverage and hydrolyzed formula (eHF) as placebo. The “rice based formula” induced emesis, diarrhoea and lethargy. Laboratory investigations reveal an increase of absolute count of neutrophils and the presence of faecal eosinophils. The patient was treated with both intravenous hydration and steroids. According to Powell criteria, oral food challenge was considered positive and diagnosis of FPIES induced by rice beverage was made. Patient was discharged at home with the indication to avoid rice and any rice beverage as well as to reintroduce hydrolyzed formula. A case of FPIES induced by rice beverage has never been reported. The present case clearly shows that also beverage containing rice proteins can be responsible of FPIES. For this reason, the use of rice beverage as cow’s milk substitute for the treatment of non IgE-mediated food allergy should be avoided