title: Inhibition of IgE-induced activation of human mast cells by IL-10.
abstract: BACKGROUND
  IL-10 exhibits anti-inflammatory effects on activated rodent mast cells (MC) in vitro and inhibits allergen-induced airway inflammation in vivo in murine models. The effects of IL-10 on the allergic activation of human MC are presently unknown.
  
  
  OBJECTIVE
  In light of the well-known heterogeneity of mast cell reactivity between animal species, one cannot readily predict the response of human MC to IL-10. Moreover, the impact of IL-10 on MC-derived proinflammatory mediators is still unknown. Thus, the objective of this study was to investigate the effects of IL-10 on the release of inflammatory mediators by IgE/anti-IgE-challenged human cord blood-derived mast cells (CBMC), used as an in vitro model of MC phenotypically similar to human lung MC.
  
  
  METHODS
  Highly purified human MC were obtained by a first step of long-term culture of cord blood mononuclear cells in the presence of human recombinant stem cell factor (rhSCF) and of human recombinant IL-6 (rhIL-6), followed by a second step of purification by depletion of contaminating cells with an immunomagnetic
  
  
  METHODS
  The cells were treated with human IgE, then challenged with anti-human IgE, in the presence or the absence of recombinant rhIL-10 used at various concentrations. Histamine, tumour necrosis factor-alpha (TNF-alpha), IL-5 and IL-8 were measured in the various supernatants collected at different times after the beginning of the challenge.
  
  
  RESULTS
  IL-10 inhibited the release of TNF-alpha and of IL-8, but not of IL-5, by activated CBMC. Interestingly, IL-10 also inhibited the release of histamine by activated CBMC, contrasting with data reported for rodent MC.
  
  
  CONCLUSIONS
  These findings suggest that IL-10 might have anti-inflammatory effects on IgE/anti-IgE-challenged human MC by inhibiting their release of TNF-alpha, IL-8 and histamine. These data provide new insights into the control of human mast cell activation and might lead to a better knowledge of the cellular mechanisms controlling allergic reactions.
authors: Department of Pharmacology, Faculty of Medicine and Pharmacy, Besançon, France.
authors: B
authors: B
authors: Royer
authors: S
authors: S
authors: Varadaradjalou
authors: P
authors: P
authors: Saas
authors: J J
authors: JJ
authors: Guillosson
authors: J P
authors: JP
authors: Kantelip
authors: M
authors: M
authors: Arock
mesh_terms: D018929:Cell Culture Techniques; D002470:Cell Survival / Q000187:drug effects; D004306:Dose-Response Relationship, Immunologic; D005312:Fetal Blood / Q000166:cytology; D006636:Histamine Release / Q000187:drug effects / Q000276:immunology; D006801:Humans; D006967:Hypersensitivity / Q000188:drug therapy / Q000503:physiopathology; D007073:Immunoglobulin E / Q000494:pharmacology*; D018836:Inflammation Mediators / Q000494:pharmacology; D016753:Interleukin-10 / Q000494:pharmacology*; D015848:Interleukin-5 / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism; D008407:Mast Cells / Q000166:cytology / Q000187:drug effects* / Q000276:immunology*; D011994:Recombinant Proteins / Q000276:immunology / Q000378:metabolism / Q000494:pharmacology; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000187:drug effects
chemical_list: D018836:Inflammation Mediators; D015848:Interleukin-5; D016209:Interleukin-8; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D007073:Immunoglobulin E