title: Desensitizing mice to ovalbumin through subcutaneous microsphere immunotherapy (SMITH).
abstract: BACKGROUND
  We investigated whether subcutaneously-injected, biodegradable, poly (D,L-lactic-co-glycolic) acid (PLGA) microspheres loaded with ovalbumin (OVA) were able to down-regulate the T helper 2 (TH2) response in mice that were sensitized to this protein, and whether this response was dose-dependent.
  
  
  METHODS
  PLGA microspheres were created using a double emulsion technique. Female BALB/c mice were sensitized to OVA and then assigned to receive subcutaneous microsphere immunotherapy (SMITH) using either blank microspheres (n = 4), low-dose OVA-loaded microspheres (n = 5), or high-dose OVA-loaded microspheres (n = 5). Antigen-specific immunoglobulin E (IgE) in serum was measured at day 0 (prior to sensitization), day 14 (prior to immunization), and days 28 and 42 (after immunization).
  
  
  RESULTS
  All mice were successfully sensitized to OVA. In the group receiving blank microspheres, there was a continual rise in antigen-specific IgE from Day 14 to Day 42, which was statistically significant. In the group receiving low-dose OVA-loaded microspheres, there was a statistically significant drop in the antigen-specific IgE levels from Day 14 to Day 28, but overall no significant change in IgE level when looking at the Day 14 to Day 42 interval. A similar pattern of antibody level changes was seen in the group receiving high-dose OVA-loaded microspheres, but the decrease from Day 14 to Day 28 was not statistically significant.
  
  
  CONCLUSIONS
  Our data suggest that SMITH has the ability to downregulate the production of antigen-specific IgE in a food allergy model, and this observation in our study was not dose-dependent. Its potential use in the treatment of IgE-mediated allergic disease warrants further investigation.
authors.affiliation: Department of Otorhinolaryngology, Weill Cornell Medical College, New York, NY, USA. wir2011@med.cornell.edu
authors.forename: William R
authors.initials: WR
authors.lastname: Reisacher
authors.forename: Dara
authors.initials: D
authors.lastname: Liotta
authors.forename: Sara
authors.initials: S
authors.lastname: Yazdi
authors.forename: David
authors.initials: D
authors.lastname: Putnam
mesh_terms: D000818:Animals; D001672:Biocompatible Materials / Q000494:pharmacology; D003888:Desensitization, Immunologic / Q000379:methods*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005240:Feasibility Studies; D005260:Female; D007073:Immunoglobulin E / Q000097:blood*; D019344:Lactic Acid / Q000494:pharmacology; D051379:Mice; D008807:Mice, Inbred BALB C; D008863:Microspheres; D010047:Ovalbumin / Q000276:immunology*; D010865:Pilot Projects; D011100:Polyglycolic Acid / Q000494:pharmacology; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D006377:T-Lymphocytes, Helper-Inducer / Q000378:metabolism*
chemical_list: D001672:Biocompatible Materials; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D007073:Immunoglobulin E; D010047:Ovalbumin