Publication: Nisinin Tek Başına ve Amikasin, Seftazidim ve İmipenemle Olan Kombinasyonlarının Polimorf Nüveli Lökosit Fonksiyonlarına Etkisi
Abstract
isinin (32µg/mL) tek başına ve terapötik konsantrasyonlarındaki amikasin (21µg/mL), seftazidim (42µg/mL) ve imipenem (50µg/mL) ile olan kombinasyonlarının sağlıklı gönüllü PNL fonksiyonları (fagositoz ve hücre içi öldürme aktivitesi) üzerine etkisi in vitro koşullarda, yaş ortalaması 25 olan 20 sağlıklı gönüllüde araştırılmıştır. PNL'ler (1x107 hücre/mL) EDTA'lı venöz kandan ficoll-hypaque gradient yöntemi ile ayrılmıştır. Fagositoz ve hücre içi öldürme aktivitesi tayininde Alexander ve arkadaşlarının yöntemi değiştirilerek kullanılmıştır. Tek başına nisin ve nisinin, amikasin, seftazidim ve imipenem ile olan kombinasyonlarının, sağlıklı gönüllü PNL'lerinin fagositik ve hücre içi öldürme aktivitesini kontrole göre anlamlı olarak azalttığı saptanmıştır (p<0.001). Sonuç olarak; tek başına nisin ve nisinin, amikasin, seftazidim ve imipenem ile olan kombinasyonları PNL fonksiyonları üzerine inhibitör etki gösterirken, terapötik konsantrasyonlarındaki tek başına amikasin, seftazidim ve imipenem PNL fonksiyonlarını olumsuz etkilememiştir. Bulgularımız, infeksiyon hastalıklarının tedavisi başarısı açısından son derece önemli olan, rasyonel antimikrobiyal ajan seçiminde PNL fonksiyonlarının önemli bir etkisinin olabileceğini göstermektedir. Bu immünolojik olayın açıklanması için ilave çalışmalar yapılmalıdır.
The objective of this study was to investigate the effect of antimicrobial cationic peptide nisin (32µg/mL) at minimal inhibitory concentration (MIC) alone in combination with amikacin (21µg/mL), ceftazidime (42µg/mL) and imipenem (50µg/mL) at therapeutic concentrations and their combinations with nisin on polymorphonuclear leukocyte (PMN) functions (phagocytosis and intracellular killing activity) were examined in vitro on 20 healthy volunteers whose mean age was 25. PMNs (1x107cells/mL) were isolated by ficoll-hypaque gradient centrifugation method from venous blood with ethylene diaminetetraacetic acid (EDTA). Phagocytosis and intracellular killing activity were assayed by modifying Alexander's method. It was observed that nisin, nisin+amikacin, nisin+ceftazidime and nisin+imipenem combinations significantly decreased phagocytosis and intracellular killing activity of PMNs in healthy volunteers when compared with the control (p<0.001).Consequently, while nisin alone and in combination with amikacin, ceftazidime, and imipenem showed inhibitory activity on PMN functions, amikacin, ceftazidime and imipenem at therapeutic concentraions does not impair normal PMN function.The finding of our study shows the importance of PMN functions for its potential influence in decision of rational antimicrobial selection is extremely important for success of therapy. Additional studies are necessary to elucidate the nature of these immunologic phenomenon.
The objective of this study was to investigate the effect of antimicrobial cationic peptide nisin (32µg/mL) at minimal inhibitory concentration (MIC) alone in combination with amikacin (21µg/mL), ceftazidime (42µg/mL) and imipenem (50µg/mL) at therapeutic concentrations and their combinations with nisin on polymorphonuclear leukocyte (PMN) functions (phagocytosis and intracellular killing activity) were examined in vitro on 20 healthy volunteers whose mean age was 25. PMNs (1x107cells/mL) were isolated by ficoll-hypaque gradient centrifugation method from venous blood with ethylene diaminetetraacetic acid (EDTA). Phagocytosis and intracellular killing activity were assayed by modifying Alexander's method. It was observed that nisin, nisin+amikacin, nisin+ceftazidime and nisin+imipenem combinations significantly decreased phagocytosis and intracellular killing activity of PMNs in healthy volunteers when compared with the control (p<0.001).Consequently, while nisin alone and in combination with amikacin, ceftazidime, and imipenem showed inhibitory activity on PMN functions, amikacin, ceftazidime and imipenem at therapeutic concentraions does not impair normal PMN function.The finding of our study shows the importance of PMN functions for its potential influence in decision of rational antimicrobial selection is extremely important for success of therapy. Additional studies are necessary to elucidate the nature of these immunologic phenomenon.