title: Venom immunotherapy induces monocyte activation.
abstract: BACKGROUND
  Venom immunotherapy (VIT) is an efficient treatment of hymenoptera venom allergy. The mechanism of VIT is based on the induction of tolerance of allergen-specific Th2 cells. The mechanisms of this T cell modulation are unknown, and could depend on cytokines produced by other cell types such as interleukin (IL)-12, tumour necrosis factor (TNF)-alpha and IL-10 by monocytes.
  
  
  OBJECTIVE
  To assess if VIT modifies the monocyte production of IL-12, TNF-alpha and IL-10 during the 45 first days of treatment.
  
  
  METHODS
  Fourteen patients and seven controls were included. Blood samples were taken once in controls and at day (D)1, D30 and D45 of VIT in patients. Monocytes were isolated, cultured with and without lipopolysaccharide (LPS), and the culture supernatant was harvested. IL-10, IL-12 and TNF-alpha were assayed in supernatants by ELISA.
  
  
  RESULTS
  Baseline cytokine levels were not statistically different between patients and controls. During treatment, an increase of spontaneous monocyte production of IL-12 and TNF-alpha was observed at D15 and D45. The production of IL-10 increased at D15 and D45 but not significantly. After LPS-stimulation, IL-12, TNF-alpha and IL-10 monocyte production was not modified by VIT.
  
  
  CONCLUSIONS
  VIT induces a monocyte activation characterized by a delayed overproduction of IL-12 and TNF-alpha. These cytokines could be relevant to the inhibition of Th2 cells during VIT. Therefore, VIT-induced tolerance could depend not only on the specific action of venom antigens on T cells, but also on a secondary non-specific action of monocytes.
authors.affiliation: UPRES 2050, Groupe de Recherche Clinique 'Pathologie respiratoire liée à l'environnement', Service de Pneumo-Allergologie, INSERM, Assistance Publique Hôpitaux de Marseille, Hôpital Ste Marguerite, Marseilles, France. amagnan@mail.ap-hm.fr
authors.forename: A
authors.initials: A
authors.lastname: Magnan
authors.forename: V
authors.initials: V
authors.lastname: Marin
authors.forename: L
authors.initials: L
authors.lastname: Mély
authors.forename: J
authors.initials: J
authors.lastname: Birnbaum
authors.forename: S
authors.initials: S
authors.lastname: Romanet
authors.forename: P
authors.initials: P
authors.lastname: Bongrand
authors.forename: D
authors.initials: D
authors.lastname: Vervloet
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D001514:Bee Venoms / Q000276:immunology / Q000627:therapeutic use*; D002478:Cells, Cultured; D003888:Desensitization, Immunologic / Q000379:methods*; D005260:Female; D006801:Humans; D006927:Hymenoptera; D016753:Interleukin-10 / Q000096:biosynthesis; D018664:Interleukin-12 / Q000096:biosynthesis; D008262:Macrophage Activation; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000276:immunology* / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis; D014862:Wasp Venoms / Q000276:immunology / Q000627:therapeutic use*
chemical_list: D001514:Bee Venoms; D014409:Tumor Necrosis Factor-alpha; D014862:Wasp Venoms; D016753:Interleukin-10; D018664:Interleukin-12