Antibiotics and production of granulocyte-macrophage colony-stimulating factor by human bronchial epithelial cells in vitro. A comparison of cefodizime and ceftriaxone.
Cultured human bronchial epithelial cells (HBEC) produce both granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin 8 (IL-8). The influence of cefodizime (CAS 69739-16-8), a new broad spectrum cephalosporin with immunostimulatory effects, and ceftriaxone on the production of GM-CSF and IL-8 in HBEC primary cultures was investigated. HBEC were isolated from biopsy specimens obtained during fibreoptic bronchoscopy in 12 patients (most frequent diagnosis: chronic bronchitis). Confluent monolayers of HBEC cultured on collagen were incubated for 24 h in a medium without study drugs (spontaneous production) or containing cefodizime or ceftriaxone at the clinically relevant concentrations of 1, 10 and 100 mg/l, with or without tumor necrosis factor alpha (TNF alpha, 100 U/ml). GM-CSF and IL-8 were measured in supernatant by ELISA technique. TNF alpha alone led to a significant (p < 0.005) increase in both GM-CSF and IL-8 production. Cefodizime induced a significant (p < 0.05), dose-dependent increase in GM-CSF release. No additive effect of cefodizime with TNF alpha was observed. Cefodizime did not affect IL-8 production and ceftriaxone had no influence on cytokine production. This is the first report of a stimulatory effect of a beta-lactam antibiotic on cytokine production by epithelial cells. GM-CSF production by epithelial cells is an important immunological step for neutrophil and monocyte recruitment and cell priming during lung defence. Previous studies with cefodizime in immunodepressed subjects have shown activation of phagocytosis and phagocytosis-related functions in non-lung phagocytes. An indirect mechanism of action, similar to that indicated by our results, may have been responsible for these stimulatory effects.(ABSTRACT TRUNCATED AT 250 WORDS)
Pacheco
Y
Y
Service de Pneumologie, Hôpital Lyon-Sud, France.
Hosni
R
R
Dagrosa
E E
EE
Gormand
F
F
Guibert
B
B
Chabannes
B
B
Lagarde
M
M
Perrin-Fayolle
M
M
D000368:Aged; D001980:Bronchi / Q000187:drug effects / Q000378:metabolism*; D002439:Cefotaxime / Q000031:analogs & derivatives* / Q000494:pharmacology; D002443:Ceftriaxone / Q000494:pharmacology*; D002478:Cells, Cultured; D004797:Enzyme-Linked Immunosorbent Assay; D004848:Epithelium / Q000187:drug effects / Q000378:metabolism; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000096:biosynthesis*; D006801:Humans; D016209:Interleukin-8 / Q000096:biosynthesis; D008297:Male; D008875:Middle Aged; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D016209:Interleukin-8; D014409:Tumor Necrosis Factor-alpha; D002443:Ceftriaxone; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D002439:Cefotaxime; C033356:cefodizime