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IL-18 is a recently characterised cytokine which induces IFN-γ synthesis from T cells and synergizes with IL-12 to promote differentiation of T helper (Th)1 cells. There is evidence to suggest that airway inflammation in asthma is associated with a Th-2 profile, characterised by IL4 and IL5 production. In contrast, the immune response in sarcoid appears to show Th1 polarisation. The precise mechanisms for divergence in CD4 response in these diseases are not known. We questioned if IL 18 may be implicated in the differentiation of T helper cells in these disease processes. Methods: BAL were obtained from 11 asthmatics, 15 sarcoid patients and 13 normal subjects. Mean ages (SD) and FEV1 were 47.5(10.5) and 77.1 (14.5)%; 39.9(18.0)y and 94.8(18.0)%; and 49.5(17.3)y and 98.8(4.6)% respectively for asthmatics, sarcoids and normal subjects. Asthma was diagnosed in accord with ATS guidelines. All asthmatics were on inhaled steroids (800-2000 mcg/day), two were on oral steroids. The diagnosis of sarcoidosis was supported by lung biopsy histology in all apart from two where ACE levels were markedly elevated. All sarcoid patients had typical radiographic appearances. IL-18 levels were measured in BAL and supernatant of stimulated alveolar macrophages (with 0-100 ng/ml of LPS) using an in-house ELISA assay. Total and differential cell counts in BAL were performed in all samples. Results: IL18 levels were significantly lower in BAL from patients with asthma compared to sarcoid and normal controls- median (+/- I Q range) levels of 0.0 (0.0-0.0) pg/ml compared to 222.0 (110-340) pg/ml in sarcoid patients (p=0.009, Mann Whitney Rank Sum test) and 162 (38-203) pg/ml in normal controls (p=0.025, Mann Whitney Rank Sum test). There was no correlation between IL-18 levels and BAL macrophage counts, nor between IL-18 and lymphocyte count. No relationship was found between steroid dose and IL 18 levels. We found significant increase in IL-18 production with progressive stimulation of alveolar macrophages in sarcoid patients but not in asthma or normal subjects. Conclusion: The findings suggest that lack of IL-18 in asthmatic airways may contribute to Th2 mediated airway inflammation. This loss may be secondary to a decrease in IL-18 production from alveolar macrophages. Our data is concordant with a recent study which showed enhanced allergen-induced eosinophilia in IL18 deficient mice (Kodama T et al. JACI 2000).


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