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短期阿奇霉素治疗对慢性阻塞性肺疾病中性粒细胞及炎症标志物的调节作用

Modulation of neutrophil and inflammation markers in chronic obstructive pulmonary disease by short-term azithromycin treatment.

作者信息

Parnham Michael J, Culić Ognjen, Eraković Vesna, Munić Vesna, Popović-Grle Sanja, Barisić Karmela, Bosnar Martina, Brajsa Karmen, Cepelak Ivana, Cuzić Snjezana, Glojnarić Ines, Manojlović Zoran, Novak-Mircetić Renata, Oresković Katarina, Pavicić-Beljak Verica, Radosević Senka, Sucić Mirna

机构信息

PLIVA Research Institute Ltd, Prilaz baruna Filipovića 29, HR-10 000 Zagreb, Croatia.

出版信息

Eur J Pharmacol. 2005 Jul 4;517(1-2):132-43. doi: 10.1016/j.ejphar.2005.05.023.

Abstract

The anti-inflammatory potential of azithromycin in chronic obstructive pulmonary disease (COPD) patients was explored following a standard oral dosing regimen. Patients with moderate and severe COPD were treated with azithromycin (500 mg, n=16) or placebo (n=8) once daily for 3 days in a randomized, double blind design, to compare effects on inflammation markers with those seen in a previous study in healthy volunteers. A battery of tests was made on serum, blood neutrophils and sputum on days 1 (baseline), 3, 4, 11, 18 and 32. In comparison to placebo, azithromycin resulted in an early transient increase in serum nitrites plus nitrates (day 3), associated with a tendency towards an increase in the blood neutrophil oxidative burst to phorbol myristic acetate. Subsequently, prolonged decreases in blood leukocyte and platelet counts, serum acute phase protein (including C reactive protein) and soluble E-selectin and blood neutrophil lactoferrin concentrations and a transient decrease in serum interleukin-8 were observed. Blood neutrophil glutathione peroxidase activity showed a prolonged increase after azithromycin treatment. The biphasic facilitatory-then-inhibitory response to azithromycin seen in healthy volunteers is not so clearly detectable in COPD patients, only potential anti-inflammatory effects. Treatment for longer periods may give therapeutic anti-inflammatory benefit in these patients.

摘要

按照标准口服给药方案,对阿奇霉素在慢性阻塞性肺疾病(COPD)患者中的抗炎潜力进行了探索。中重度COPD患者采用随机双盲设计,接受阿奇霉素(500毫克,n = 16)或安慰剂(n = 8)治疗,每日一次,持续3天,以比较其对炎症标志物的影响与之前在健康志愿者中进行的一项研究的结果。在第1天(基线)、第3天、第4天、第11天、第18天和第32天对血清、血液中性粒细胞和痰液进行了一系列检测。与安慰剂相比,阿奇霉素导致血清亚硝酸盐加硝酸盐早期短暂升高(第3天),同时血液中性粒细胞对佛波醇肉豆蔻酸酯的氧化爆发有增加趋势。随后,观察到血液白细胞和血小板计数、血清急性期蛋白(包括C反应蛋白)、可溶性E选择素以及血液中性粒细胞乳铁蛋白浓度持续下降,血清白细胞介素-8短暂下降。阿奇霉素治疗后,血液中性粒细胞谷胱甘肽过氧化物酶活性持续增加。在COPD患者中,未像在健康志愿者中那样明显检测到阿奇霉素的双相促进-然后抑制反应,仅显示出潜在的抗炎作用。对这些患者进行更长时间的治疗可能会带来治疗性抗炎益处。

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