Determination of cytokine release after in vivo and in vitro administration of Deodan (a preparation from Lactobacillus bulgaricus "LB51") by the rabbit pyrogen test.
We investigated the in vivo and in vitro cytokine inducing effects of Deodan, an oral preparation from Lactobacillus bulgaricus "LB-51", using the rabbit pyrogen test. In the first experimental approach we administered Deodan, or its chromatographically purified fraction, via the i.m. or i.v. routes. Low doses of Deodan i.m. caused the formation of a single temperature peak, whereas large doses produced a biphasic temperature curve. Intravenous injection of Deodan produced a monophasic fever in all tested doses. Chromatographically purified Deodan injected i.v. to rabbits caused a febrile response with a dose-dependent pattern, strikingly similar to that of lipopolysaccharide. LAL-testing of Deodan, however, showed that the preparation does not contain endotoxin. In in vivo neutralization studies we demonstrated that IL-1, TNF alpha, and IL-6 mediate the rabbit febrile response to Deodan. Interestingly, the effects of Deodan on the production of TNF alpha and IL-6 were more pronounced than its IL-1 inducing activity. In the second approach, we injected supernatants from mononuclear cells incubated with nonpyrogenic doses of Deodan, intravenously to rabbits ("monocyte type" of pyrogen test). Rapid-onset monophasic fevers were observed, typical for the rabbit pyrogen reaction to i.v. administration of exogenous IL-1 and TNF. Finally, we demonstrated the presence of pyrogenic cytokines in the supernatants from macrophages of Deodan-treated mice. Together, these results indicate that Deodan induces the production of cytokines with endogenous pyrogenic activity.
Guencheva
G
G
Institute for State Control of Drugs, Sofia, Bulgaria.
Popova
P
P
Davidkova
G
G
Mincheva
V
V
Mihailova
S
S
Bogdanov
A
A
Pacelli
E
E
Auteri
A
A
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D001426:Bacterial Proteins / Q000494:pharmacology; D002473:Cell Wall / Q000737:chemistry; D016207:Cytokines / Q000378:metabolism*; D005334:Fever / Q000139:chemically induced; D006020:Glycopeptides / Q000494:pharmacology*; D007778:Lactobacillus / Q000737:chemistry*; D008070:Lipopolysaccharides; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008813:Mice, Inbred ICR; D011817:Rabbits
D000276:Adjuvants, Immunologic; D001426:Bacterial Proteins; D016207:Cytokines; D006020:Glycopeptides; D008070:Lipopolysaccharides