The effects of amphotericin B, fluconazole and miconazole on neutrophil and lymphocyte function in a guinea pig model.

We studied the effects of amphotericin B, fluconazole and miconazole on guinea pig neutrophil and lymphocyte function. Neutrophil adherence, chemotaxis, and deoxyglucose uptake and mitogen-induced lymphocyte proliferation were examined. The drugs were administered intraperitoneally in varying dosages based on those used therapeutically, either as a single infusion or daily for 3 days. Miconazole at high dosage (60 mg/kg) suppressed mitogen-induced lymphocyte proliferation, otherwise a single dose of any of the drugs had no effect on neutrophil or lymphocyte function irrespective of concentration used. Variable stimulative or suppressive effects on neutrophil and lymphocyte function were observed after three daily doses of each drug, but there was no dose-response pattern and the effects were erratic. The data show that, contrary to previous findings in vitro, amphotericin B, fluconazole and miconazole were not consistently immunosuppressive in vivo in this animal model.

Modulation of human neutrophil adherence by oral bacteria.

Polymorphonuclear neutrophils (PMNs) comprise over 90 per cent of leukocytes in the oral cavity. Although these phagocytic cells have primary defence roles in the gingiva, their stimulation by micro-organisms may also cause substantial tissue damage due to the release of lysosomal enzymes and oxygen radicals. Adherence of PMNs to the endothelium and their subsequent diapedesis and egress to areas of infection are considered early vital events in the inflammatory process. In this study, oral bacteria were screened to determine their direct effects on PMN activation using an in vitro method of measuring PMN adherence to Dacron fibres. Most of the bacteria investigated increased PMN adherence, indicating their potential to cause tissue damage through the release of PMN lysosomal enzymes and other products. In contrast, Bacteroides species suppressed PMNs, indicating their ability to circumvent the phagocytic cells, thus gaining a potential advantage in dental colonization. The modulatory effects of oral bacteria on PMN activation may have significant roles in the immunopathogenesis of oral disease.

Effect of human milk and infant milk formulae on adherence of Giardia intestinalis.

Human milk was shown to inhibit adherence of Giardia at concentrations as low as 0.5%. Unsaturated fatty acids were also found to cause significant inhibitory effects on adherence, with ED50 values less than 1 microM for arachidonic, linoleic and palmitic acids. A variety of infant feeding formulae derived from cow's milk and soy bean had suppressive effects on adherence. These observations may explain in part the low prevalence of giardiasis in young infants.

Inhibition of adherence of Giardia intestinalis by human neutrophils and monocytes.

Human neutrophils and monocytes were found to be capable of interfering with the in vitro adherence of Giardia intestinalis. Significantly greater inhibition of adherence was shown by stimulated phagocytic cells than by unstimulated cells. Both azurophil and specific granules extracted from the cytoplasm of neutrophils were equally potent in their adherence inhibitory activity. Dose-dependent effects on adherence were observed with granular enzymes and reactive oxygen species. Lower concentrations of reactive oxygen species were required for adherence inhibition that for growth inhibition. These results suggest that the adherence mechanism of G. intestinalis may be a feasible target for immunological attack by phagocytic cells.

Sensitivity in vitro of Giardia intestinalis to dyadic combinations of azithromycin, doxycycline, mefloquine, tinidazole and furazolidone.

The new macrolide antibiotic, azithromycin, produced significant growth inhibition of Giardia intestinalis at 100 micrograms/ml, but adherence inhibition was significant at concentrations as low as 1 microgram/ml for the two strains used in these experiments. The dyadic combinations of azithromycin-furazolidone, doxycycline-mefloquine, doxycycline-tinidazole and mefloquine-tinidazole were synergistic for inhibition of adherence. These results suggest that these dyadic combinations may be worthy of consideration for chemotherapy of recalcitrant giardiasis.