title: Reduced production of interleukin 12 by interferon gamma primed alveolar macrophages from atopic asthmatic subjects.
abstract: BACKGROUND
  Asthma is characterised pathologically by an inflammatory pulmonary infiltrate rich in T helper (Th) 2 cells and eosinophils. Interleukin (IL)-12 is a heterodimeric cytokine critical for driving the development of uncommitted Th cells to express a Th 1 phenotype. Reduced pulmonary production of IL-12 may therefore play a role in the pathogenesis of asthma by contributing to the pulmonary cytokine imbalance seen in asthma.
  
  
  METHODS
  IL-12 p70 protein levels in bronchoalveolar lavage fluid and p70 protein levels and IL-12 messenger RNA in alveolar macrophage cultures from normal and atopic asthmatic subjects were measured.
  
  
  RESULTS
  There was a significant difference between the mean IL-12 p70 protein level in the bronchoalveolar lavage fluid from asthmatic subjects (37.5 pg/ml) and from normal subjects (131 pg/ml, p = 0.04). Alveolar macrophages from asthmatic subjects produced significantly less IL-12 protein (30 pg/ml) and messenger RNA than those from normal subjects (69.5 pg/ml, p<0.005). These differences were not caused by inhibition of IL-12 production by IL-10 nor to generalised hyporesponsiveness of asthmatic alveolar macrophages from subjects to the effects of interferon (IFN)-gamma.
  
  
  CONCLUSIONS
  Pulmonary IL-12 production is lower in asthmatic subjects. This reduction is not the result of generalised hyporesponsiveness to IFN-gamma. Reduced IL-12 levels may contribute to the development of asthmatic pulmonary inflammation through dysregulation of Th cell development.
authors.affiliation: Lung Research Group, University of Bristol, Medical School Unit, Southmead Hospital, Westbury on Trym, Bristol BS10 5NB, UK.
authors.forename: M J
authors.initials: MJ
authors.lastname: Plummeridge
authors.forename: L
authors.initials: L
authors.lastname: Armstrong
authors.forename: M A
authors.initials: MA
authors.lastname: Birchall
authors.forename: A B
authors.initials: AB
authors.lastname: Millar
mesh_terms: D000328:Adult; D000368:Aged; D001249:Asthma / Q000378:metabolism*; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology; D018664:Interleukin-12 / Q000378:metabolism*; D016676:Macrophages, Alveolar / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000378:metabolism
chemical_list: D012333:RNA, Messenger; D018664:Interleukin-12; D007371:Interferon-gamma