Pseudomonas aeruginosa was studied for its effects on T-cell-mediated responses in mice, as exemplified by anti- Listeria immunity and delayed-type hypersensitivity to sheep erythrocytes. Immunity to Listeria monocytogenes was measured by quantitation of bacteria in spleens and mortality; delayed hypersensitivity to sheep erythrocytes was tested by the footpad reaction. Three different preparations of P. aeruginosa were used: the supernatant of a heat-killed culture, living bacteria, and heat-killed organisms. Similar results were obtained with the three preparations. Administration of P. aeruginosa 24 h before Listeria infection reduced the resistance to the secondary challenge, as measured by increased bacterial multiplication in the spleen and rate of mortality. Cell transfer experiments showed that pretreatment of normal recipient mice with P. aeruginosa prevented them from being adoptively immunized against a Listeria challenge infection with spleen cells from immune donors. They also showed that treatment of donors with P. aeruginosa before immunization affected the capacity of their spleen cells to protect normal recipients against Listeria. Furthermore, spleen and peritoneal exudate cells obtained from mice given P. aeruginosa were capable of preventing immunization of normal recipients against Listeria. Similar results were obtained when the delayed hypersensitivity response to sheep erythrocytes was studied. The suppressive activity of P. aeruginosa -treated spleen cells was lost by removing adherent cells. Conversely, the adherent, heat-killed, anti-immunoglobulin-treated spleen cells exerted a suppressor effect. It thus appears that P. aeruginosa injection changes macrophage and T-lymphocyte activities and results in the development of adherent, macrophage-like suppressor cells in the spleen and peritoneal cavity.

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We previously demonstrated the suppression of cell-mediated immunity to Listeria monocytogenes by Pseudomonas aeruginosa-induced, macrophage-like cells. The present study was undertaken to evaluate the mechanism for this suppression. P. aeruginosa supernatant was shown to activate macrophages by the criteria of increased bactericidal capacities and increased attachment to glass surfaces. Acquired cellular resistance to L. monocytogenes could also be inhibited by macrophages from L. monocytogenes-pretreated mice. The depression of acquired immunity by P. aeruginosaor L. monocytogenes-activated macrophages did not appear to be due to a reduction of antigenic stimulus after nonspecific macrophage activation. In contrast, our findings suggest that suppression is mediated by activated macrophages through a prostaglandin-dependent mechanism. In vivo administration of aspirin blocked the immunosuppressive effect of P. aeruginosaor L. monocytogenes-activated cells. Moreover, the suppressive activity of supernatants of macrophages from Listeria-infected mice was reversed when indomethacin was present during supernatant generation. Finally, prostaglandin El treatment in vivo profoundly inhibited the induction of cell-mediated immunity to L. monocytogenes. The possible role and mechanism of prostaglandin in suppressing cellular immunity to intracellular bacteria are discussed. * Corresponding author. natants from these cells. Finally, our results demonstrated that prostaglandin E1 (PGE1) treatment in vivo profoundly disturbs the development of acquired immunity to L. monocytogenes. This study provides in vivo evidence that activated macrophages via arachidonic acid metabolites can suppress CMI to intracellular bacteria. MATERIALS AND METHODS Mice. Female Swiss CD-1 mice from Charles River Breeding Laboratories, Inc., Wilmington, Mass., were used

The killing kinetics of cefotaxime and fosfomycin, alone and in combination, against seven clinical isolates of penicillin-resistant pneumococci were studied. The antibiotics were tested at 1 x, 2 x and 4 x the MIC for each individual isolate. The results showed a synergic interaction of the two antibiotics for three of the seven strains. This strategy may be useful clinically.

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