title: Anti-inflammatory activity of sublingual immunoglobulin (SLIG) in a murine model of allergen-driven airway inflammation.
abstract: OBJECTIVE
  Intravenous immunoglobulin (IVIG) displays anti-inflammatory activities in many diseases. Subcutaneous administration of anti-IgE in humans provides benefit in severe persistent allergic asthma. Given the well established efficacy of sublingual allergen immunotherapy in respiratory type I allergies, we investigated the therapeutic potential of sublingual immunoglobulin (SLIG), most particularly anti-IgE SLIG, in a murine model of allergen-driven airway inflammation.
  
  
  METHODS
  BALB/c mice sensitized with ovalbumin (OVA) were treated sublingually with rat monoclonal IgG1 or IgG2a, either directed to mouse IgE or with no reported specificity. Airway hyperresponsiveness (AHR) was assessed by whole body plethysmography, and eosinophil infiltrates were characterized in bronchial alveolar lavages (BAL). OVA-specific antibody and T cell responses were analyzed in sera and saliva or lung and draining lymph nodes, by ELISA or CBA measurement of cytokine production, respectively.
  
  
  RESULTS
  AHR and BAL eosinophil infiltrates were substantially decreased in mice treated sublingually with particulate OVA (positive control), as well as in animals receiving various rat IgG1, irrespective of their specificity for murine IgE. In contrast, no improvement was observed in mice treated with PBS (negative control) or various rat IgG2a. SLIG anti-inflammatory activity is not related to a downregulation of Th2, Th17 or an induction of Foxp3(+) CD4(+) regulatory T cell responses. Mass spectrometry analysis of glycan moieties, such as sialic acid, suggests that the differential efficacy of rat IgG1 and IgG2a is not related to their capacity to interact with lectins borne by oral immune cells.
  
  
  CONCLUSIONS
  In a murine model of allergen-driven airway inflammation, SLIG exhibits an anti-inflammatory activity irrespective of the immunoglobulin specificity, and in the absence of allergen. As a noninvasive approach, SLIG deserves to be further studied as a treatment for other inflammatory diseases beyond allergic asthma.
authors: Stallergenes, 6 rue Alexis de Tocqueville, 92160 Antony, France. tbatard@stallergenes.com
authors: T
authors: T
authors: Batard
authors: A
authors: A
authors: Zimmer
authors: E
authors: E
authors: Nony
authors: J
authors: J
authors: Bouley
authors: S
authors: S
authors: Airouche
authors: S
authors: S
authors: Luce
authors: M
authors: M
authors: Turfkruyer
authors: S
authors: S
authors: Tourdot
authors: L
authors: L
authors: Mascarell
authors: P
authors: P
authors: Moingeon
mesh_terms: D000286:Administration, Sublingual; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage*; D000888:Antibodies, Anti-Idiotypic / Q000008:administration & dosage*; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D004804:Eosinophils / Q000276:immunology; D005260:Female; D006801:Humans; D006967:Hypersensitivity / Q000628:therapy*; D007074:Immunoglobulin G / Q000008:administration & dosage*; D007167:Immunotherapy / Q000379:methods*; D008168:Lung / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D010047:Ovalbumin / Q000276:immunology; D010993:Plethysmography, Whole Body; D012140:Respiratory Tract Diseases / Q000628:therapy*; D016896:Treatment Outcome
chemical_list: D000893:Anti-Inflammatory Agents; D000888:Antibodies, Anti-Idiotypic; D000911:Antibodies, Monoclonal; D007074:Immunoglobulin G; C026408:anti-IgE antibodies; D010047:Ovalbumin