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)

Concentrations of cefodizime in bronchial secretions after single intravenous administration.

UNLABELLED: The concentrations of cefodizime (HR 221, CAS 69739-16-8) in bronchial secretions were measured after administration of a single intravenous bolus of 2 g in 19 patients requiring fibreoptic bronchoscopy for diagnostic purposes or as therapeutic follow-up. These concentrations, which were obtained in absence of inflammation of the mucosa, were compared to serum concentrations obtained simultaneously. The penetration into bronchial secretions was rapid, maximum levels of between 1 and 5 mg/kg being already observed 1 h after injection. Most concentrations remained about 1 mg/kg throughout the whole observation period of about 5.5 h. The percent penetration amounted to about 1.5% of the corresponding serum concentrations. CONCLUSION: Concentrations well above the MIC90s of the relevant respiratory pathogens--S. pneumoniae, M. catarrhalis, H. influenzae, K. pneumoniae--and Enterobacteriaceae were reached in bronchial secretions after intravenous injection of a single 2 g dose of cefodizime. Even higher levels may be expected in the usual condition of inflamed bronchial mucosa as found in respiratory infections.

Influence of experimental rhinitis on the gonadotropin response to intranasal administration of buserelin.

The influence of experimental rhinitis on the absorption of buserelin, measured as the serum luteinizing hormone (LH) response, has been investigated. A single dose of 200 micrograms buserelin was given to 24 healthy male volunteers after induction of experimental rhinitis with histamine and after use of a saline spray (placebo control). Except on one occasion, when the pump-spray apparently was incorrectly operated, serum LH concentration rose after buserelin. There was no difference in the LH response between histamine-induced rhinitis and saline controls. It was concluded that intranasal application of buserelin represents a reliable mode of application and that modification of the administration route or a change in the dosage schedule during naturally-occurring nasal inflammations, such as the common cold and allergic rhinitis, is unnecessary in patients undergoing chronic treatment with intranasal buserelin, e.g. for prostatic cancer, endometriosis, precocious puberty, and contraception.