A study of immunomodulatory effects of moxifloxacin, ciprofloxacin and clarithromycin on human cells

Isolated mononuclear cells from 20 healthy volunteers were incubated for 4 hours with varying concentrations of the antibiotics either in the absence of presence of PMA, ionomycin and monesin. Both moxifloxacin (0-50μg/ml) and ciprofloxacin (0-100μg/ml) dose-dependently decrease the Th1 signature cytokine IFNγ and IL-4 (a signature cytokine for Th2 cells) (p=0.001) and only IL4 was affected by clarithromycin (p=0.04, 0-125μg/ml). However, the overall ratio of Th1 to Th2 cells was not found to be significantly modulated in cells treated with any of concentrations of the three antibiotics. The findings of the immunomodulatory effects of ciprofloxacin clarithromycin and moxifloxacin strongly implicate transcription factors as major targets of the antibiotics. An investigation of the effect of ciprofloxacin and moxifloxacin on the expression of genes and proteins of leucocytes was undertaken utilising. Affymetrix genechip and protein array analysis. Venous blood was drawn from a healthy volunteer and aliquots were incubated for 4 hours in the presence or absence of 2μ/ml LPS with concentrations of ciprofloxacin (0-50μg/ml) or moxifloxacin (0-20μg/ml). Leuocytes and plasma were isolated from the whole blood and were taken forward to gene and protein array analysis respectively. These revealed that both ciprofloxacin and moxifloxacin are capable of significantly modulating the expressions of a wide range of immune related factors at all the variable concentrations in both endotoxin stimulated and unstimulated whole blood. In particular the array studies revealed that the quinoline drugs were capable of modulating chemoattractant factors which could potentially enhance the inflammatory response and prime cells to migrate to the site of infection, suggesting that early use of the antibiotics may be beneficial. Continued enhanced inflammatory responses could, on the other hand be damaging to patient recovery and survival.EThOS - Electronic Theses Online ServiceGBUnited Kingdo