Azithromycin suppresses activation of nuclear factor-kappa B and synthesis of pro-inflammatory cytokines in tracheal aspirate cells from premature infants.
Nuclear factor-kappaB (NF-kappaB) plays a central role in regulating key proinflammatory mediators. The activation of NF-kappaB is increased in tracheal aspirate (TA) cells from premature infants developing bronchopulmonary dysplasia (BPD). We studied the effect of azithromycin (AZM) on the suppression of NF-kappaB activation and the synthesis of pro-inflammatory cytokines IL-6 and IL-8 by TA cells obtained from premature infants. Tracheal aspirate cells were stimulated with tumor necrosis factor-alpha (TNF-alpha) and incubated with AZM. The nuclear NF-kappaB-DNA binding activity, the levels of inhibitory kappaB-alpha (IkappaB-alpha) in the cytoplasmic fraction and IL-6 and IL-8 release in the cell culture media were measured. Stimulation of TA cells by TNF-alpha increased the activation of NF-kappaB, which was suppressed by the addition of AZM. Increased activation of NF-kappaB was also associated with increased levels of pro-inflammatory cytokines (IL-6 and IL-8). AZM significantly reduced the IL-6 and IL-8 production to the levels similar to control. TNF-alpha stimulation also increased the degradation of IkappaB-alpha, which was restored with the addition of AZM. Our data suggest that AZM therapy may be an effective alternative to steroids in reducing lung inflammation and prevention of BPD in ventilated premature infants.
Department of Pediatrics, Cooper University Hospital-Robert Wood Johnson Medical School, Camden, New Jersey 08103, USA. aghai-zubair@cooperhealth.edu
Zubair H
ZH
Aghai
Aruna
A
Kode
Judy G
JG
Saslow
Tarek
T
Nakhla
Sabeena
S
Farhath
Gary E
GE
Stahl
Riva
R
Eydelman
Louise
L
Strande
Paola
P
Leone
Irfan
I
Rahman
D000900:Anti-Bacterial Agents / Q000494:pharmacology* / Q000627:therapeutic use; D017963:Azithromycin / Q000494:pharmacology* / Q000627:therapeutic use; D001997:Bronchopulmonary Dysplasia / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control; D002452:Cell Count; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D005260:Female; D005865:Gestational Age; D006801:Humans; D020672:I-kappa B Proteins / Q000378:metabolism; D007231:Infant, Newborn; D007234:Infant, Premature / Q000378:metabolism*; D015850:Interleukin-6 / Q000096:biosynthesis*; D016209:Interleukin-8 / Q000096:biosynthesis*; D008297:Male; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000378:metabolism*; D012121:Respiration, Artificial / Q000009:adverse effects; D013396:Suction; D014132:Trachea / Q000378:metabolism* / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D000900:Anti-Bacterial Agents; D020672:I-kappa B Proteins; C508600:IL6 protein, human; D015850:Interleukin-6; D016209:Interleukin-8; D016328:NF-kappa B; C000606204:NFKBIA protein, human; D014409:Tumor Necrosis Factor-alpha; D000072000:NF-KappaB Inhibitor alpha; D017963:Azithromycin