Effects of FK-506 on the course of murine salmonellosis.
Bacterial infections are a major threat to immunocompromised patients. Therefore, the effect of immunosuppression with cyclosporin A and FK-506 on the course of murine salmonellosis was tested. Treatment of mice with both substances reduced the amount of circulating CD4+ T-cells and CD8+ T-cells in uninfected and infected mice. The substances effectively suppressed the proliferation of spleen cells of treated mice upon activation with concanavalin A (ConA) and upon activation by mouse peritoneal macrophages infected with live salmonellae, but left the response to lipopolysaccharide (LPS) unaltered. In particular, treatment of mice with nontoxic doses led to an increase in Salmonella typhimurium counts in the organs of primarily infected mice from day 14 onward, but not in the early phase of infection. In mice treated during secondary infection with S. typhimurium the bacterial counts in the organs were increased from day 3 of infection onward. We conclude that both substances aggravate murine salmonellosis, most likely by inhibition of T-cell function. Patients receiving FK-506 might also be, therefore, at risk of salmonella infection.
Nichterlein
T
T
Institute of Medical Microbiology and Hygiene, Faculty of Clinical Medicine Mannheim, University of Heidelberg, Mannheim, Germany.
Kretschmar
M
M
Geginat
G
G
Hirth
K
K
Altenburg
H P
HP
Hof
H
H
D000818:Animals; D000907:Antibodies, Bacterial / Q000276:immunology; D015169:Colony Count, Microbial; D016572:Cyclosporine / Q000494:pharmacology* / Q000633:toxicity; D005260:Female; D007166:Immunosuppressive Agents / Q000494:pharmacology* / Q000633:toxicity; D008070:Lipopolysaccharides / Q000276:immunology; D051379:Mice; D008805:Mice, Inbred A; D012481:Salmonella Infections, Animal / Q000276:immunology*; D012486:Salmonella typhimurium / Q000187:drug effects* / Q000276:immunology; D013154:Spleen / Q000166:cytology / Q000187:drug effects*; D016559:Tacrolimus / Q000494:pharmacology* / Q000633:toxicity
D000907:Antibodies, Bacterial; D007166:Immunosuppressive Agents; D008070:Lipopolysaccharides; D016572:Cyclosporine; D016559:Tacrolimus