Systemic anti-inflammatory mediators in COPD: increase in soluble interleukin 1 receptor II during treatment of exacerbations.
BACKGROUND
The aim of this study was to test the hypothesis that the chronic inflammatory process present in chronic obstructive pulmonary disease (COPD) is due to a defective endogenous anti-inflammatory mechanism.


METHODS
Systemic levels of the anti-inflammatory mediators soluble interleukin 1 receptor II (sIL-1RII), soluble tumour necrosis factor receptor p55 (sTNF-R55) and sTNF-R75, and of C reactive protein (CRP) and lipopolysaccharide binding protein (LBP) were analysed in 55 patients with stable COPD (median forced expiratory volume in one second (FEV(1)) 34% predicted (range 15-78)) and compared with levels in 23 control subjects. In addition, changes in these mediators were studied in 13 patients with COPD (median FEV(1) 34% predicted (range 19-51)) during the first 7 days in hospital with an exacerbation of the disease.


RESULTS
Patients with stable COPD were characterised by a systemic inflammatory process indicated by an increased leucocyte count (7.2 (4.7-16.4) v 4.8 (3.5-8.3) x 10(9)/l), raised levels of CRP (11.8 (1.1-75.0) v 4.1 (0.6-75.0) microg/ml) and LBP (45.6 (8.1-200.0) v 27.9 (14.1-71.5) microg/ml), and moderate increases in both sTNF-Rs. In contrast, the sIL-1RII level did not differ between patients and controls (4.53 (2.09-7.60) v 4.63 (3.80-5.93) ng/ml). During treatment of disease exacerbations, systemic levels of both CRP (at day 3) and LBP (at day 7) were significantly reduced compared with day 1, whereas sIL-1RII levels increased.


CONCLUSIONS
These data suggest an imbalance in systemic levels of pro- and anti-inflammatory mediators in patients with stable COPD. The increase in the anti-inflammatory mediator sIL-1RII during treatment of exacerbations may contribute to the clinical improvement.
Dentener
M A
MA
Department of Pulmonology and Surgery, Maastricht University, Nutrition and Toxicology Research Institute Maastricht (NUTRIM), 6202 AZ Maastricht, The Netherlands. Mieke.Dentener@pul.unimaas.nl
Creutzberg
E C
EC
Schols
A M
AM
Mantovani
A
A
van't Veer
C
C
Buurman
W A
WA
Wouters
E F
EF
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015703:Antigens, CD / Q000032:analysis; D002352:Carrier Proteins; D002908:Chronic Disease; D002373:Cyclic AMP Receptor Protein / Q000032:analysis; D004268:DNA-Binding Proteins / Q000032:analysis; D005260:Female; D005541:Forced Expiratory Volume / Q000502:physiology; D006801:Humans; D008173:Lung Diseases, Obstructive / Q000378:metabolism* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D017472:Receptors, Interleukin-1 / Q000378:metabolism*; D053574:Receptors, Interleukin-1 Type II; D018124:Receptors, Tumor Necrosis Factor / Q000032:analysis; D047888:Receptors, Tumor Necrosis Factor, Type I; D047889:Receptors, Tumor Necrosis Factor, Type II; D015398:Signal Transduction; D014157:Transcription Factors; D014797:Vital Capacity / Q000502:physiology
D015703:Antigens, CD; D002352:Carrier Proteins; D002373:Cyclic AMP Receptor Protein; D004268:DNA-Binding Proteins; D017472:Receptors, Interleukin-1; D053574:Receptors, Interleukin-1 Type II; D018124:Receptors, Tumor Necrosis Factor; D047888:Receptors, Tumor Necrosis Factor, Type I; D047889:Receptors, Tumor Necrosis Factor, Type II; D014157:Transcription Factors; C085968:UBP1 protein, human