Reduced interleukin-18 levels in BAL specimens from patients with asthma compared to patients with sarcoidosis and healthy control subjects.
OBJECTIVE
To investigate whether differing airway interleukin (IL)-18 levels may be implicated in the pathogenesis of asthma and sarcoidosis.


METHODS
University teaching hospital.


METHODS
IL-18 levels were measured in BAL fluid and in the supernatant of lipopolysaccharide (LPS)-stimulated alveolar macrophages obtained by BAL from 15 patients with sarcoidosis, 11 patients with asthma, and 13 healthy subjects. We also examined the relationship between IL-18 levels and macrophage and lymphocyte concentrations in BAL fluid. IL-18 was measured using an in-house enzyme-linked immunosorbent assay.


RESULTS
IL-18 levels were significantly lower in BAL fluid from patients with asthma (median, 0.0 pg/mL; interquartile range, 0.0 to 0.0 pg/mL) compared to patients with sarcoidosis (median, 222.0 pg/10(6); interquartile range, 110 to 340 pg/mL; p = 0.009, Mann Whitney rank-sum test) and healthy control subjects (median, 162 pg/mL; interquartile range, 38 to 203 pg/mL; p = 0.025, Mann Whitney rank-sum test). Individual analyses comparing IL-18 levels with BAL macrophage counts, and IL-18 with lymphocyte counts in the three groups showed no correlation between these indexes. The mean levels of IL-18 in unstimulated macrophage supernatants were 410 pg/10(6) cells for patients with asthma, 723.4 pg/10(6) cells for patients with sarcoidosis, and 734.8 pg/10(6) cells for healthy control subjects (p > 0.05). Stimulated macrophages from patients with sarcoidosis responded with increasing amounts of IL-18 at lower doses of LPS than macrophages from healthy control subjects or patients with asthma.


CONCLUSIONS
Our findings suggest that inherently low levels of IL-18 may be associated with the pathogenesis of asthmatic airway inflammation.
Ho
Ling-Pei
LP
Osler Chest Unit, Churchill Hospital, Oxford, UK. Ling-Pei.Ho@imm.ox.ac.uk
Davis
Margaret
M
Denison
Alan
A
Wood
Fraser T
FT
Greening
Andrew P
AP
D000328:Adult; D001249:Asthma / Q000378:metabolism*; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry* / Q000166:cytology; D002452:Cell Count; D002478:Cells, Cultured; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D020382:Interleukin-18 / Q000032:analysis*; D008214:Lymphocytes; D008264:Macrophages; D016676:Macrophages, Alveolar / Q000378:metabolism; D008875:Middle Aged; D017565:Sarcoidosis, Pulmonary / Q000378:metabolism*
D020382:Interleukin-18