Reduced production of interleukin 12 by interferon gamma primed alveolar macrophages from atopic asthmatic subjects

Background-Asthma is characterised pathologically by an inflammatory pulmon ary 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 product ion of IL-12 may therefore play a role in the pathogenesis of asthma by con tributing to the pulmonary cytokine imbalance seen in asthma. Methods-IL-12 p70 protein levels in bronchoalveolar lavage fluid and p70 pr otein levels and IL-12 messenger RNA in alveolar macrophage cultures from n ormal and atopic asthmatic subjects were measured. Results-There was a significant difference between the mean IL-12 p70 prote in 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/m l) 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 pulmo nary inflammation through dysregulation of Th cell development.