title: Intranasal administration of IL-35 inhibits allergic responses and symptoms in mice with allergic rhinitis.
abstract: BACKGROUND
  IL-35 was recently identified as an anti-inflammatory cytokine. We previously reported that recombinant fusion protein of murine IL-35 and human IgG1 Fc fragment (rIL-35) reduced Th2 cytokines (IL-4 and IL-5) in vitro. However, it is unclear whether IL-35 can attenuate nasal allergic responses and symptoms of allergic rhinitis in vivo.
  
  
  METHODS
  To investigate the in vivo effect of IL-35 on allergic rhinitis in mice, mice were sensitized with ovalbumin (OVA). Intranasal administration of rIL-35 and intranasal challenge of OVA were then performed. Nasal symptoms were estimated after the last nasal challenge. Nasal tissue and cervical lymph nodes (CLN) were collected. OVA-specific IgE in sera, OVA-specific T cell response, and the production of cytokines (IL-4, IL-5, and IL-10) stimulated by the OVA antigen were measured. The transcription level of Foxp3 and the frequency of CD4+CD25+regulatory T cells were also measured.
  
  
  RESULTS
  rIL-35 significantly inhibited the number of sneezes and nasal rubbing movements. It also reduced the number of eosinophils in the nasal mucosa and significantly decreased the level of OVA-specific IgE, the OVA-specific T cell proliferation, and the production of IL-4 and IL-5. Furthermore, rIL-35 significantly increased the production of IL-10, the transcription level of Foxp3, and the frequency of CD4+CD25+regulatory T cells.
  
  
  CONCLUSIONS
  This study showed for the first time that rIL-35 inhibits nasal allergic responses and symptoms in mice, and that rIL-35 increases IL-10, Foxp3, and CD4+CD25+regulatory T cells in CLN. This study also suggests that intranasal administration of IL-35 can attenuate allergic rhinitis.
authors.affiliation: Department of Otorhinolaryngology, Nagoya City University, Aichi, Japan. Electronic address: suzu-mo@med.nagoya-cu.ac.jp.
authors.forename: Motohiko
authors.initials: M
authors.lastname: Suzuki
authors.affiliation: Department of Otorhinolaryngology, Nagoya City University, Aichi, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Yokota
authors.affiliation: Department of Otorhinolaryngology, Nagoya City University, Aichi, Japan.
authors.forename: Yoshihisa
authors.initials: Y
authors.lastname: Nakamura
authors.affiliation: Department of Otorhinolaryngology, Nagoya City University, Aichi, Japan.
authors.forename: Shinya
authors.initials: S
authors.lastname: Ozaki
authors.affiliation: Department of Otorhinolaryngology, Nagoya City University, Aichi, Japan.
authors.forename: Shingo
authors.initials: S
authors.lastname: Murakami
mesh_terms: D000281:Administration, Intranasal; D000818:Animals; D016207:Cytokines / Q000096:biosynthesis; D004195:Disease Models, Animal; D007073:Immunoglobulin E / Q000097:blood / Q000276:immunology; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology; D007378:Interleukins / Q000008:administration & dosage*; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D051379:Mice; D009297:Nasal Mucosa / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D010641:Phenotype; D011993:Recombinant Fusion Proteins; D065631:Rhinitis, Allergic / Q000175:diagnosis* / Q000188:drug therapy / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism; D016896:Treatment Outcome
chemical_list: D016207:Cytokines; D007074:Immunoglobulin G; D007378:Interleukins; D011993:Recombinant Fusion Proteins; C569375:interleukin-35, mouse; D007073:Immunoglobulin E
keywords: Allergic rhinitis; Cervical lymph node; IL-10; IL-35; Regulatory T cell