Food allergen-sensitized CCR9+ lymphocytes enhance airways allergic inflammation in mice.

BACKGROUND: The mechanisms of the atopic march, characterized by a natural progression from food and cutaneous allergies to rhinitis and asthma, are still unknown. However, as several organs can be involved, chemokines and their receptors might be implicated in this process and may be instrumental factors. OBJECTIVES: We hypothesized that the T-cell gut-homing receptor CCR9 could be implicated in the evolution of allergic diseases. METHODS: We characterized the immune response and the role of CCR9 in a murine model combining food allergy to wheat gliadin and a model of acute airways inflammation in response to house dust mite. RESULTS: Compared with solely asthmatic-like mice, we demonstrated that the aggravation of pulmonary symptoms in consecutive food and respiratory allergies, characterized by an increase in pulmonary resistance and a higher Th17/Treg ratio, was abrogated in CCR9 knockout mice. Moreover, transfer of food-allergic CD4+ T cells from wild-type but not from CCR9-/- aggravated airways inflammation demonstrating that CCR9 is involved in food allergy-enhanced allergic airway inflammation to unrelated allergens. CONCLUSION: Taken together, our results demonstrated a crucial role of the T-cell homing receptor CCR9 in this model and validated its potential for use in the development of therapeutic strategies for allergic diseases.

Chemokine receptors in allergic diseases.

Under homeostatic conditions, as well as in various diseases, leukocyte migration is a crucial issue for the immune system that is mainly organized through the activation of bone marrow-derived cells in various tissues. Immune cell trafficking is orchestrated by a family of small proteins called chemokines. Leukocytes express cell-surface receptors that bind to chemokines and trigger transendothelial migration. Most allergic diseases, such as asthma, rhinitis, food allergies, and atopic dermatitis, are generally classified by the tissue rather than the type of inflammation, making the chemokine/chemokine receptor system a key point of the immune response. Moreover, because small antagonists can easily block such receptors, various molecules have been developed to suppress the recruitment of immune cells during allergic reactions, representing potential new drugs for allergies. We review the chemokines and chemokine receptors that are important in asthma, food allergies, and atopic dermatitis and their respectively developed antagonists.

Maternal exposure to GOS/inulin mixture prevents food allergies and promotes tolerance in offspring in mice.

BACKGROUND: Food allergies affect 4-8% of children and are constantly on the rise, thus making allergies a timely issue. Most importantly, prevention strategies are nonexistent, and current therapeutic strategies have limited efficacy and need to be improved. One alternative to prevent or reduce allergies, particularly during infancy, could consist of modulating maternal immunity and microbiota using nondigestible food ingredients, such as prebiotics. For this purpose, we studied the preventive effects of prebiotics in Balb/c mothers during pregnancy and breastfeeding on food allergy development in offspring mice. METHODS: After weaning, the offspring from mothers that were exposed to GOS/inulin mixture or fed a control diet were intraperitoneally sensitized to wheat proteins to induce a systemic allergic response and orally exposed to the same allergen. Immunological, physiological, and microbial parameters were analyzed. RESULTS: GOS/inulin mixture diet modified the microbiota of mothers and their offspring. Offspring from mothers that received GOS/inulin prebiotics were protected against food allergies and displayed lower clinical scores, specifically of IgE and histamine levels, compared to offspring from mothers fed a control diet. Moreover, GOS/inulin supplementation for the mother resulted in stronger intestinal permeability in the offspring. Enhancement of the regulatory response to allergic inflammation and changes in the Th2/Th1 balance toward a dampened Th2 response were observed in mice from GOS/inulin mixture-exposed mothers. CONCLUSION: The treatment of pregnant and lactating mice with nondigestible GOS/inulin prebiotics promotes a long-term protective effect against food allergies in the offspring.

[Action of a sodium lactate perfusion on the hemodynamic effects of beta-blockaders]. / Action d'une perfusion de lactate de soude sur les effets hémodynamiques de bêta-bloquants.

In 15 dogs who had been given propranolol and 5 humans who had been given Pindolol, an infusion of sodium lactate produced: 1) an increased in blood lactate levels and pH; 2) an increase in the cardiac index; 3) a state in which an infusion of isoproterenol (inactive on its own) could act as it would have done had the betaadrenergic receptors not been blocked. A perfusion of lactic acid which was sufficient to cause the variations in pH and blood lactate levels that are seen with exercise had no action on the heart rate nor on the cardiac index of 10 dogs treated with propranolol and could not re-establish the betastimulating properties of isoproterenol. Finally, alkalosis produced by an infusion of THAM in 13 dogs or sodium bicarbonate in 2 humans, changed neither the cardiac index nor the heart rate, nor the response to isoproterenol after a betaadrenergic blockade. Infusion of sodium lactate associated with isoproterenol could be used to combat the depressent effects of betablockers in patients with cardiac disorders.

[A hospital cancer registry. Breast cancer, 1977]. / Registro hospitalario de cáncer. Cáncer de mama, 1977.

The clinical histories of the patients studied in the National Institute of Oncology in 1977 were reviewed in relation to breast cancer in women, that was found in 52.5% of them. 50% were comprised between 40 and 60 years of age, 68.3% were diagnosed within the first year after the presentation of clinical symptoms. 30.6% of the patients had a localized tumor, while all the others showed regional lymph node involvement and/or distant metastases. Malignancy was confirmed histologically in 90 per 100 of the cases; 41.5% were carcinomas, 27.9% corresponding to the infiltrating duct carcinoma type. Therapy could be applied to 80% of the patients with a curative purpose, while in 20% was only palliative. Including those women with previous treatments in other medical centers before coming to the National Institute of Oncology, the treatment applied was surgery in 90%, radiotherapy in 60% and chemotherapy in 20% of the cases. Five-year survival was 43% (28% clinically free of disease, and 15% with symptoms of disease).

[The hospital cancer registry. A study of the cases registered in 1977]. / Registro hospitalario de cáncer. Estudio de los casos registrados en 1977.

The authors describe the results of the hospital registry of tumors made at the National Institute of Oncology in Madrid, following the rules given by the cancer specialists of the World Health Organization. The studied cases correspond to the cancer patients that were seen during the year 1977 for the first time.