Sputum tumour necrosis factor-alpha and leukotriene concentrations in cystic fibrosis.
It is postulated that a vigorous host inflammatory response in the cystic fibrosis lung contributes to lung injury. Tumour necrosis factor-alpha (TNF-alpha) may play a part in that process and in the generation of leukotrienes. Therefore, the relationships between sputum TNF-alpha, leukotriene concentration, and lung function abnormalities in 16 children with cystic fibrosis were investigated. Each subject provided sputum samples and performed spirometry. TNF-alpha was measured by enzyme linked immunosorbent assay; individual leukotrienes were separated using high performance liquid chromatography and quantified by radioimmunoassay. The geometric mean concentration of TNF-alpha was 129.7 pg/ml and 95% confidence interval 48.2 to 348.3. Mean (SEM) leukotriene B4 (LTB4) was 97.8 (22.9) pmol/g and total cysteinyl leukotrienes were 60.9 (14.8) pmol/g. Mean (SD) forced expiratory volume in one second (FEV1) of the group was 53 (15)% of predicted and forced vital capacity (FVC) was 65 (14)% of predicted. There was a significant positive correlation between TNF-alpha and both LTB4 and the total cysteinyl leukotriene sputum content. An inverse relationship existed between TNF-alpha and FEV1 and FVC. Moreover, a negative correlation was observed between sputum LTB4 and FEV1 and FVC. These results suggest that TNF-alpha and the leukotrienes may participate in the airways inflammation and airflow obstruction observed in cystic fibrosis subjects and support the hypothesis that TNF-alpha upregulates the 5-lipoxygenase pathway in vivo.
Greally
P
P
Department of Thoracic Medicine, King's College Hospital, London.
Hussein
M J
MJ
Cook
A J
AJ
Sampson
A P
AP
Piper
P J
PJ
Price
J F
JF
D000293:Adolescent; D002648:Child; D003550:Cystic Fibrosis / Q000378:metabolism* / Q000503:physiopathology; D005260:Female; D005541:Forced Expiratory Volume; D006801:Humans; D007975:Leukotriene B4 / Q000032:analysis; D015289:Leukotrienes / Q000032:analysis*; D008297:Male; D013183:Sputum / Q000737:chemistry*; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis*; D014797:Vital Capacity
D015289:Leukotrienes; D014409:Tumor Necrosis Factor-alpha; D007975:Leukotriene B4