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Female mice are more susceptible to the development of allergic airway inflammation than male mice
Authors:B N Melgert †  D S Postma†  I Kuipers  M Geerlings †  M A Luinge †  B W A van der  Strate †  H A M Kerstjens†  W Timens  M N Hylkema
Institution:Department of Pathology and Laboratory Medicine, University Hospital Groningen, Groningen, The Netherlands. B.N.Melgert@path.umcg.nl
Abstract:BACKGROUND: In humans the prevalence of asthma is higher among females than among males after puberty. The reason for this phenomenon is not clear. OBJECTIVE: We tested the hypothesis that female mice are more susceptible to the development of allergic asthma than male mice and studied allergic immune responses in the lung. METHODS: We compared allergic airway inflammation, i.e. methacholine (MCh) responsiveness, serum IgE, and cytokines, and the number of the different leucocytes in lungs of male and female BALB/c mice, twice-sensitized to ovalbumin (OVA) and subsequently challenged with OVA (OVA-mice) or phosphate-buffered saline (PBS-mice) aerosols on days 24-26, 30, and 31. RESULTS: OVA challenge significantly increased MCh responsiveness, numbers of eosinophils, CD4(+) T cells, CD4(+)/CD25(+) T cells, B cells, and levels of Thelper (Th)2 cytokines, total, and OVA-specific IgE. There was, however, also an effect of gender, with female mice responding to OVA challenges with higher numbers of eosinophils, CD4(+) T cells, B cells, and levels of IL-4, IL-13, IFN-gamma, total, and OVA-specific IgE than male mice. In contrast, female PBS-mice had significantly lower percentages of regulatory CD4(+)/CD25(+) T cells than males (females 4.2+/-0.2% vs. males 5.3+/-0.1% of CD4(+) T cells, P<0.05). CONCLUSION: Female mice develop a more pronounced type of allergic airway inflammation than male mice after OVA challenge. The reduced percentage of regulatory T cells in the lungs of female PBS-mice may indicate that the level of these cells in the lung during the sensitization phase is important for the development and/or progression of an allergic immune response after multiple OVA challenges.
Keywords:airway hyper-responsiveness  allergy  asthma  eosinophils  females  gender  IgE  ovalbumin  regulatory T cells  sex hormones
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