Naslov
The effect of vasoactive intestinal peptide on production of tumor necrosis factor-a in vivo

Autori
Čulo, Filip ; Erceg, Damir ; Viik, Pal

Izvornik
International journal of immunotherapy (0255-9625) 14 (1998), 2; 83-87

Vrsta, podvrsta i kategorija rada
Radovi u časopisima, članak, znanstveni

Ključne riječi
vasoactive intestinal peptide; cAMP; tumor necrosis factor-alpha

Sažetak
There are increasing body of data showing that vasoactive intestinal peptide (VIP) acts as an immunomodulator and that it inhibits a variety of lymhocyte and macrophage function. It was shown that mononuclear cells have specific receptors for VIP and VIP increases the level of cAMP in these cells. Since several agents that increase cAMP level in mononuclear cells inhibit the production of tumor necrosis factor-a (TNF-a), we investigated the production of TNF-a in mice that were pretreated with VIP. The effect of VIP on TNF-a production was determined in in three different experimental models. In the first model, saline or VIP (2 ug per mouse i.p) were given to normal mice 15 minutes before they were given lipoplysaccharide (LPS) i.v. (10 ug per mouse). In the second model, the VIP or saline and LPS were given at the same doses and shedule in mice given 18 days before i.v. 1.5 mg of BCG (living bacteria, Institute Pasteur). In both models, TNF-a was determined in serum taken from mice 90 minutes after LPS injection. In the third model, mice were infected with E. coli (3x108 bacteria i.v., strain B6, Sigma) and VIP (2 mg per mouse) or saline were given i.p. 15 minutes later. The serum for TNF-a determination two and half hours after bacteria injection. In all models, TNF-a was determined in pooled sera obtained from 4-6 mice per group, by bioassay with L929 sensitive cells. In all three models, TNF-a level was 4 to 15 times lower in mice pretreated with VIP than in control mice pretreated in saline. In further experiments, we are investigating the dose- and time-response to VIP, as well as the effect of VIP on survival of mice treated as in second and third model.

Izvorni jezik
Engleski

Znanstvena područja
Farmacija

POVEZANOST RADA