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Cefodizime modulates in vitro tumor necrosis factor-alpha, interleukin-6 and interleukin-8 release from human
F Meloni1, P Ballabio, L Bianchi
1Chair of Chemotherapy, University of Pavia, Italy.
Abstract:
Among third-generation cephalosporins, cefodizime (CFDZ) has shown to modulate many functions of the host defense system against infections. The aim of the present study was to assess the in vitro CFDZ-dependent modulation of interleukin (IL)-6, tumor necrosis factor-alpha (TNF-alpha) and IL-8 release from lipopolysaccharide (LPS)-stimulated human peripheral mononuclear cells (MNCs). Two other third-generation cephalosporins: ceftriaxone (CFX) and ceftazidime (CFT), were also tested under the same experimental conditions. At concentrations ranging from 200 to 50 micrograms/ml, CFDZ significantly decreased TNF-alpha and IL-6 release from maximally (LPS 1 microgram/ml) stimulated MNCs (42% inhibition of TNF-alpha release with 100 micrograms/ml of CFDZ). On the other hand, CFDZ revealed a marked stimulatory effect on IL-8 release (200 micrograms/ml of CFDZ induced 51.5% enhancement of IL-8 release). On the contrary, both CFX and CFT failed to exert any significant effect on TNF-alpha, IL-6 or IL-8 release.
Insights
Cefodizime modulates immune responses by decreasing tumor necrosis factor-alpha and interleukin-6 release while increasing interleukin-8 release from human cells. Other cephalosporins showed no significant effect.
Area of Science:
- Immunology
- Pharmacology
- Microbiology
Background:
- Third-generation cephalosporins, like cefodizime (CFDZ), are known to influence host defense mechanisms.
- Understanding the immunomodulatory effects of antibiotics is crucial for managing infections.
Purpose of the Study:
- To investigate the in vitro effects of cefodizime on the release of key inflammatory cytokines.
- To compare cefodizime's immunomodulatory activity with other third-generation cephalosporins, ceftriaxone and ceftazidime.
Main Methods:
- Human peripheral mononuclear cells (MNCs) were stimulated with lipopolysaccharide (LPS).
- Cytokine release (IL-6, TNF-alpha, IL-8) was measured in the presence of varying concentrations of cefodizime, ceftriaxone, and ceftazidime.
- Statistical analysis was performed to determine significant modulations.
Main Results:
- Cefodizime significantly inhibited the release of tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) in a dose-dependent manner.
- Cefodizime demonstrated a notable stimulatory effect on interleukin-8 (IL-8) release.
- Ceftriaxone and ceftazidime did not produce significant changes in the release of TNF-alpha, IL-6, or IL-8.
Conclusions:
- Cefodizime exhibits distinct immunomodulatory properties, suppressing pro-inflammatory cytokines while enhancing IL-8.
- These findings suggest that cefodizime may uniquely impact the host immune response compared to ceftriaxone and ceftazidime.
- Further research is warranted to explore the clinical implications of cefodizime's immunomodulatory effects.