RESUMO
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.
Assuntos
Azitromicina/uso terapêutico , Inflamação/tratamento farmacológico , Neutrófilos/efeitos dos fármacos , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Adulto , Idoso , Anti-Inflamatórios/uso terapêutico , Biomarcadores/sangue , Contagem de Células Sanguíneas , Proteína C-Reativa/metabolismo , Contagem de Células , Método Duplo-Cego , Selectina E/sangue , Glutationa/sangue , Glutationa Peroxidase/sangue , Fator Estimulador de Colônias de Granulócitos e Macrófagos/sangue , Granulócitos/efeitos dos fármacos , Granulócitos/fisiologia , Humanos , Inflamação/sangue , Interleucina-6/sangue , Interleucina-8/sangue , Lactoferrina/sangue , Masculino , Pessoa de Meia-Idade , Neutrófilos/metabolismo , Nitratos/sangue , Nitritos/sangue , Projetos Piloto , Doença Pulmonar Obstrutiva Crônica/sangue , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Explosão Respiratória/efeitos dos fármacos , Testes de Função Respiratória , Proteína Amiloide A Sérica/metabolismo , Escarro/citologia , Escarro/efeitos dos fármacos , Fatores de Tempo , Resultado do Tratamento , Fator de Necrose Tumoral alfa/metabolismoRESUMO
Effects on human neutrophils and circulating inflammatory mediators were studied in 12 volunteers who received azithromycin (500 mg/day, p.o.) for 3 days. Blood was taken 1 h before treatment, 2.5, 24 h and 28 days after the last dose. An initial neutrophil degranulating effect of azithromycin was reflected in rapid decreases in azurophilic granule enzyme activities in cells and corresponding increases in serum. The oxidative response to a particulate stimulus was also acutely enhanced. These actions were associated with high plasma and neutrophil drug concentrations. A continuous fall in chemokine and interleukin-6 serum concentrations, within the non-pathological range, accompanied a delayed down-regulation of the oxidative burst and an increase in apoptosis of neutrophils up to 28 days after the last azithromycin dose. Neutrophils isolated from blood at this time point still contained detectable drug concentrations. Acute neutrophil stimulation could facilitate antibacterial effects of azithromycin, while delayed, potentially anti-inflammatory activity may curtail deleterious inflammation.
