Effects of antibiotics on polymorphonuclear leukocyte chemiluminescence and chemotaxis

Abstract

Polymorphonuclear leukocyte chemiluminescence and chemotaxis assays were performed on cells obtained from normal individuals and patients with defined defects in chemotaxis or chemiluminescence. After in-vitro pre-incubation with trimethoprim/sulphamethoxazole, its separate components, clindamycin and cefotaxime, normal cells showed some enhancement in chemotaxis and significant increase in chemiluminescence. There was an even more marked increase in chemotaxis when these antibiotics were incubated with cells from patients with leukocyte chemotaxic defects. When the cells from patients with chemiluminescence defects were pre-incubated with these antibiotics, there was also substantial enhancement in chemiluminescence.

Influence of six antifungal agents on the chemiluminescence response of mouse spleen cells

“…The indication is that higher concentrations have a lowering effect on the CL response, even though the reduction is not found to be significant by the (less sensitive) Dunnett's test. Although mean peak plasma levels for Bay-n-7133 in mice are between 14 and 16 ,ug/ml (19), the peak plasma level in humans is reported to be only 2.76 pLg/ml (25), a value below the concentration determined to cause a significant reduction in CL activity in our assay. In all other instances, data analyzed by both the trend test and Dunnett's test agreed.…”

“…Our data show inhibition of the CL response of mouse spleen cells with ketoconazole at concentrations of 3.0 to 20 jig/ml. Similar conflicting data have been reported for certain antibacterial agents evaluated for their effects on immune cells, including the CL response (15,16,20,21,26). The conflicting reports on the effects of antimicrobial agents on CL may be the result of different methodologies, stimulating agents, and the use of different cell species and types.…”

“…Changes in the CL response were assessed in terms of peak intensity and area under the intensity-time curve compared with appropriate diluent controls for each drug. Only amphotericin B and ketoconazole caused statistically significant lowering of the peak intensity at levels that are therapeutically attainable (mean peak plasma levels of 2 to 4 and 3.5 to 16 ,ug/ml, respectively). Although amphotericin B and ketoconazole caused reduction in the CL response, removal of the unbound drug in the preparation by centrifugation, washing, and suspension of cells in fresh drug-free medium resulted in a return of CL activity equivalent to the activity observed in cells not exposed to these agents.…”

“…However, other reports have shown conflicting results with many of these same antibacterial agents (15,16,20). Notable among these anti-* Corresponding author.…”

Interference of Antibacterial Agents with Phagocyte Functions: Immunomodulation or "Immuno-Fairy Tales"?

“…In most studies, TMP, alone or in combination, had an inhibitory effect on PMN functions. In a single study, PMN chemotaxis and chemiluminescence were increased, and this effect was also observed with PMNs with defective functions (286). Recently, brodimoprim, in which the methoxy group in position 4 of the benzyl ring of the TMP molecule is replaced by a bromine atom, was shown to display greater lipophilicity and cellular uptake than TMP and had no inhibitory effect on PMN function, whereas TMP impaired the chemiluminescence of these cells (39).…”