S. Hockertz et R. Heckenberger, TREATMENT OF AN ACUTE BACTERIAL-INFECTION WITH A COMBINATION OF ACETYLSALICYLIC-ACID IBUPROFEN AND INTERFERON-GAMMA, Arzneimittel-Forschung, 46(10), 1996, pp. 1012-1015
The bacterial infection with Listeria monocytogenes is associated with
an inhibition of the macrophage function, the first-line defense agai
nst bacterial infection. We studied the effect of acetylsalicylic acid
(ASA, CAS 50-78-2) and ibuprofen (GAS 15687-21-1) alone and in combin
ation with a suboptimal dose of recombinant interferon gamma (IFN gamm
a) on the acute infection with Listeria monocytogenes in the Balb/c mo
use. Animals were intravenously infected with a sublethal dose of List
eria 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) uni
ts 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 t
his 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 e
fficacy showed its maximum 1 h after challenge with Listeria monocytog
enes. These results suggest that ibuprofen and ASA possess antibacteri
al activity. In addition, IFN gamma significantly increases the antiba
cterial activity of ASA and ibuprofen. Presumably, these effects are d
ue to an influence on the host immune system.