Treatment of an acute bacterial infection with a combination of acetylsalicylic acid/ibuprofen and interferon gamma.
The bacterial infection with Listeria monocytogenes is associated with an inhibition of the macrophage function, the first-line defense against bacterial infection. We studied the effect of acetylsalicylic acid (ASA, CAS 50-78-2) and ibuprofen (CAS 15687-21-1) alone and in combination with a suboptimal dose of recombinant interferon gamma. (IFN gamma) on the acute infection with Listeria monocytogenes in the Balb/c mouse. Animals were intravenously infected with a sublethal dose of Listeria monocytogenes. The therapy was carried out I) at the time of the infection, II) 30 min, III) 60 min, IV) 3 h and V) 24 h post infection. Six groups of mice were treated: i) untreated control, ii) 10(4) units IFN gamma, iii) 10 mg/kg ASA, i.v.) 10 mg/kg ASA + IFN gamma, i.v.) 12 mg/kg ibuprofen, and vi) 12 mg/kg ibuprofen + IFN gamma. The data shown that treatment with ibuprofen and ASA resulted in a significant reduction of viable bacteria in spleen and liver, the main organs of this infection. In combination with low dose interferon gamma, both non-steroidal anti-inflammatory drugs (NSAID) reduced the parasite burden in the examined organs by a factor of more than 10. The therapeutic efficacy showed its maximum 1 h after challenge with Listeria monocytogenes. These results suggest that ibuprofen and ASA possess antibacterial activity. In addition, IFN gamma significantly increases the antibacterial activity of ASA and ibuprofen. Presumably, these effects are due to an influence on the host immune system.
Hockertz
S
S
Fraunhofer Department of Toxicology and Environmental Medicine, Hamburg.
Heckenberger
R
R
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use*; D001241:Aspirin / Q000627:therapeutic use*; D001424:Bacterial Infections / Q000188:drug therapy* / Q000382:microbiology; D015169:Colony Count, Microbial; D004338:Drug Combinations; D005260:Female; D007052:Ibuprofen / Q000627:therapeutic use*; D007371:Interferon-gamma / Q000627:therapeutic use*; D008088:Listeriosis / Q000188:drug therapy / Q000382:microbiology; D008099:Liver / Q000382:microbiology; D051379:Mice; D008807:Mice, Inbred BALB C; D011994:Recombinant Proteins; D013154:Spleen / Q000382:microbiology; D013997:Time Factors
D000894:Anti-Inflammatory Agents, Non-Steroidal; D004338:Drug Combinations; D011994:Recombinant Proteins; D007371:Interferon-gamma; D001241:Aspirin; D007052:Ibuprofen