beta-Lactam antibiotic modulation of murine neutrophil cytokinesis.

Fourteen cephalosporins, 11 penicillins and 1 monobactam were evaluated for their in vitro modulation of murine neutrophil cytokinesis. As a result, the beta-lactam antibiotics were placed into 6 groups based on their effect on random (R) and FMLP-directed (D) migration [Group 1 (no effect): cephalosporin C; Group 2 (R-->D decreases): cloxacillin, cefotaxime, ceftazadime, cefuroxime, cephalothin, cephapirin, cephadine, nafcillin, piperacillin, ticarcillin, ampicillin, oxacillin, aztreonam; Group 3 (R increases D-->): cephaloridine; Group 4 (R increases D increases): cefsulodin; Group 5 (R increases D decreases): cefoperazone, cefoxitin, ceftriaxone, 6-amino-penicillanic acid; Group 6 (R decreases D decreases): cefadroxil, cefazolin, penicillin G, methicillin]. Trypan blue exclusion studies showed that inhibition of R and D by Group 6 beta-lactam antibiotics is not due to overt cytotoxicity. beta-lactam antibiotics inhibiting D also increased neutrophil adherence to plastic at a concentration of 1000 microM. Finally, the [Ca++] inhibitor chlorpromazine significantly abrogates beta-lactam- and FMLP-directed migration at a test concentration of 1 microM.

Comparative therapeutic efficacy of teicoplanin and vancomycin in normal and in neutropenic mice infected with Staphylococcus haemolyticus.

This study describes the evaluation of a murine bacteraemia model for assessing antibiotic efficacy in normal and neutropenic mice infected with coagulase-negative staphylococci. In one such evaluation, it was found that there was no significant (P greater than 0.05) difference in the ability of teicoplanin or vancomycin to protect normal or neutropenic CD-1 mice, lethally-infected with Staphylococcus haemolyticus. However, about a four-fold increase of either antibiotic was needed to protect the immunocompromised animals.

Flavonoid modulation of murine neutrophil cytokinesis.

Flavonoids are known to produce a wide range of immunomodulatory effects. In this study, flavone and six hydroxylated analogues were examined for their effect on the FMLP-directed and the random migration of murine peritoneal exudate neutrophils. Flavone significantly (p less than 0.01) inhibits both directed and random migration at an assay concentration of 100 microM. In contrast, fisetin, kaempferol, chrysin, flavonol, morin and quercetin (in decreasing order of activity) significantly (p less than 0.05 to less than 0.01) enhance both directed and random migration at concentrations of 1.0 to 100 microM. Hydrophobicity does not appear to play a key role in the observed compound activity but the number and position of the hydroxyl substitutions might be important. In addition, the [Ca++] modulator chlorpromazine was found to significantly (10 microM; p less than 0.01) inhibit fisetin-enhanced FMLP-directed migration.

Comparative effect of the naphthalenic ansamycins rifamycin SV, rifampin and cyclopentylrifampicin on murine neutrophil function.

The purpose of this study was to evaluate the in vitro effect of the naphthalenic ansamycins rifamycin SV, rifampin and cyclopentylrifampicin on neutrophil degranulation and cytokinesis using murine peritoneal exudate cells. It was found that the FMLP-stimulated secretion of myeloperoxidase was significantly inhibited by 80 micrograms rifamycin SV (P less than 0.05) and cyclopentylrifampicin (P less than 0.01) per ml. Nondirected and FMLP-directed migration was significantly (P less than 0.01) inhibited by rifamycin SV and rifampin at assay concentrations above 0.31 and 5.0 micrograms/ml respectively thus confirming the low dose rifamycin effect observed by others using human neutrophils. Finally, cyclopentylrifampicin was shown to have no significant effect on nondirected or FMLP-directed neutrophil migration at assay concentrations of 1.25 to 80 micrograms per ml.