Two important parameters control skin sensitization to a xenobiotic molecule: its sensitizing potential, an intrinsic property of each chemical, and exposure. It is often difficult to quantify a patient's exposure to a given allergen, which makes it difficult to define strong allergens. Indeed, the prevalence of an allergen, as determined by patch testing, reflects not its strength but a combination of sensitizing potential and exposure. The definition of strong sensitizers is therefore mainly derived from animal experiments where it is possible to assess a sensitization threshold or the dose per square centimeter that is able to induce significant sensitization. It has been shown in a limited number of case studies, that there is a good correlation between sensitization thresholds assessed in mice by the Local Lymph Node Assay (LLNA) and those obtained in humans with the Human Repeated Insult Patch Test (HRIPT). Based on this classification, one can recognize that strong sensitizers are quite common and that the general population is exposed regularly to them. Although the strong sensitizers include a broad diversity of chemicals, they have in common the ability to rapidly modify nucleophilic residues of proteins. (c) 2008 Elsevier Masson SAS. Tous droits reserves.
Sublingual immunotherapy (SLIT) is a non-invasive and efficacious treatment for type I respiratory allergies. To identify candidate adjuvants and galenic formulations capable of inducing tolerance by the sublingual route, an initial screening was carried out using in vitro cocultures of human monocyte-derived dendritic cells and naive CD4(+) T cells. Selected molecules were subsequently tested in a murine asthma model of sublingual immunotherapy in BALB/c mice sensitized to ovalbumin. In this model, we evaluated bronchial hyperreactivity (measured by whole-body plethysmography), pulmonary inflammation (evaluated histologically), and type 2 Immoral and cellular immune responses monitored by Elisa and Elispot techniques in mice sensitized with either soluble or with adjuvant-formulated ovalbumin. Four categories of adjuvant known to increase IL-10 +/- IFN7 production by naive CD4(+) T cells (Treg/Th1) were found to enhance SLIT efficacy in vivo in these mice. These adjuvants were: vitamin D3/dexamethasone, Lactobacillus plantarum, the TLR2 agonist Pam3CSK4, and the TLR4 synthetic ligand OM-294-BA-MP. In addition, sublingual administration of ovalbumin combined with mucoadhesive maize-derived maltodextrin increased sublingual tolerance induction by targeting oral dendritic cells and ovalbumin-specific T cells in cervical and submaxillary lymph nodes. In conclusion, better understanding of specific immune responses to allergen at the level of the sublingual mucosa may lead to the development of new sublingual vaccines. In the future, such vaccines would incorporate Th1/Treg adjuvants, as well as mucoadhesive galenic formulations that target dendritic cells in the sublingual mucosa. (c) 2008 Elsevier Masson SAS. Tous droits reserves.
The aim of the present study was to analyze the short-term relationship between pollen exposure and antiallergic drug consumption in the general population, taking into account confounding factors such as atmospheric pollution and meteorological parameters. Data on the daily consumption of antiallergic drug by individuals in the Clermont-Ferrand urban area from January 1 2000 through December 31 2001 and from January 1 2002 through December 31 2003, was obtained from the French health insurance database. An episode of allergic rhinoconjunctivitis (ARC) was defined as the association of an oral antihistamine and a local-acting antiallergic drug on the same prescription. The relationship between daily changes in atmospheric pollen concentration and daily changes in the number of treated ARC cases was analyzed using time series analysis. The results showed that the risk of treated ARC increased significantly with an interquartile increase in pollen concentration for grasses (5%, P < 0.001), hazel (7%, P < 0.02), birch (7%, P < 0.001) and ash (2%, P < 0.001). The effect was significant on the same day for all except the grasses, for which the risk lasted three days. Time series studies of antiallergic drug consumption may be useful for assessing the risk of exposure to pollens in an ambulatory population. (c) 2008 Elsevier Masson SAS. Tous droits reserves.
