Influence of in vivo prednisolone on increased in vitro O2- generation by neutrophils in emphysema.
Evidence is accumulating that neutrophil-derived oxidants substantially contribute to the development of emphysema, especially in smoking individuals. It is not clear, however, why not all smokers develop emphysema. We tested the hypothesis that an abnormality in the oxidative metabolism of polymorphonuclear leucocytes (PMNs) might contribute to the development of emphysema. We investigated in vitro O2- production by peripheral PMNs in patients with stable emphysema and in healthy controls. In addition, we investigated whether in vivo prednisolone may modulate in vitro O2- production by PMNs in patients with emphysema during a stable phase of the disease. Spontaneous O2- production by PMNs was not significantly different in patients and controls. After stimulation with submaximal concentrations of calcium ionophore A23187 and phorbol myristate acetate, however, PMNs from patients with stable emphysema produced more O2- than those from healthy controls, especially in smoking subjects. Moreover, in vitro O2- generation by PMNs significantly decreased after in vivo prednisolone treatment in patients with emphysema. We suggest that our findings reflect an abnormality of PMNs, acting as one of the factors that contribute to the development of emphysema. This abnormality may, at least partially, be dampened by in vivo prednisolone treatment. These findings may provide new insights into the pathogenesis and treatment of pulmonary emphysema. Further studies on pulmonary PMNs are necessary to extend our findings.
Renkema
T E
TE
Dept of Pulmonology, University Hospital, Groningen, The Netherlands.
Postma
D S
DS
Noordhoek
J A
JA
Sluiter
H J
HJ
Kauffman
H F
HF
D000284:Administration, Oral; D000704:Analysis of Variance; D002469:Cell Separation; D002478:Cells, Cultured / Q000187:drug effects / Q000378:metabolism; D004311:Double-Blind Method; D006801:Humans; D008297:Male; D008875:Middle Aged; D009504:Neutrophils / Q000187:drug effects* / Q000378:metabolism; D010101:Oxygen Consumption / Q000187:drug effects*; D011239:Prednisolone / Q000008:administration & dosage / Q000494:pharmacology*; D011656:Pulmonary Emphysema / Q000097:blood / Q000188:drug therapy* / Q000453:epidemiology; D012907:Smoking / Q000097:blood / Q000188:drug therapy / Q000453:epidemiology; D013481:Superoxides / Q000097:blood
D013481:Superoxides; D011239:Prednisolone