Significance of the interleukin-1 receptor antagonist/interleukin-1 beta ratio as a prognostic factor in patients with pulmonary sarcoidosis.
BACKGROUND
Various factors such as serum angiotensin-converting enzyme (sACE) activity, bronchoalveolar lavage (BAL) fluid lymphocyte percent, CD4/CD8 ratio, and shadows on chest radiograph have been identified as indexes of disease activity in patients with sarcoidosis. However, it remains to be confirmed whether these factors can predict clinical outcomes.


OBJECTIVE
To examine whether the interleukin-1 receptor antagonist (IL-1ra)/IL-1 beta ratio can predict the clinical course, we prospectively followed the clinical courses of 30 patients with pulmonary sarcoidosis 4 years after measurement of immunoreactive amounts of IL-1ra or IL-1 beta in the culture supernatants obtained from BAL fluid macrophages.


METHODS
Immunoreactive amounts of IL-1ra or IL-1 beta were measured using ELISA. Changes in pulmonary function, sACE activity, and shadows on chest radiographs during observation periods were evaluated as markers of changes in disease activity.


RESULTS
We found that the patients whose shadows on chest radiographs showed improvement had a higher molar IL-1ra/IL-1 beta ratio than the patients whose shadows persistently remained 4 years after BAL examination (p < 0.05). The molar ratio was found to be positively correlated with improvement of percent vital capacity (p < 0.05) and negatively correlated with the ratio of sACE activity at the time of the last observation to sACE activity at the time of BAL (sACE(LAST)/sACE(BAL), p < 0.01). The sACE(LAST)/sACE(BAL) ratio was significantly lower in patients whose shadows on chest radiographs decreased than in those whose shadows remained unchanged (p < 0.005).


CONCLUSIONS
The IL-1ra/IL-1 beta ratio in the BAL fluid macrophage culture supernatants in patients with pulmonary sarcoidosis could be a useful marker in predicting the persistence of granulomatous lesions (chronicity).
Mikuniya
T
T
Department of Respiratory Medicine, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
Nagai
S
S
Takeuchi
M
M
Mio
T
T
Hoshino
Y
Y
Miki
H
H
Shigematsu
M
M
Hamada
K
K
Izumi
T
T
D000328:Adult; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D002478:Cells, Cultured; D005260:Female; D006801:Humans; D053590:Interleukin 1 Receptor Antagonist Protein; D008168:Lung / Q000503:physiopathology; D008264:Macrophages / Q000378:metabolism; D008297:Male; D009994:Osmolar Concentration; D007703:Peptidyl-Dipeptidase A / Q000097:blood; D011379:Prognosis; D013902:Radiography, Thoracic; D017472:Receptors, Interleukin-1 / Q000378:metabolism*; D017565:Sarcoidosis, Pulmonary / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology*; D012795:Sialoglycoproteins / Q000378:metabolism*; D013997:Time Factors
C507763:IL1RN protein, human; D053590:Interleukin 1 Receptor Antagonist Protein; D017472:Receptors, Interleukin-1; D012795:Sialoglycoproteins; D007703:Peptidyl-Dipeptidase A