Experimental studies on the bacterial product CANTASTIM derived from Pseudomonas aeruginosa. V. Protective effect in endotoxin shock

In this paper, we investigated the effect of the treatment with the bacterial immunomodulator CANTASTIM in a model of endotoxin shock in mice. Among the different mouse models described for septic shock, we have chosen the low-dose endotoxin model using D-galactosamine sensitized mice. We noticed a significant increase in the survival rate of the mice treated with CANTASTIM before the endotoxin challenge. This protective effect was correlated with a strong reduction in the level of TNF alpha in the sera of treated mice. Prior exposure to CANTASTIM also attenuated subsequent ex vivo nitric oxide production by peritoneal macrophages of the mice. In this model of endotoxin shock, the major role has been attributed to TNF alpha acting through its receptor TNFRI (p55). A downregulation of this receptor as a consequence of the treatment with CANTASTIM may be hypothesized. However, the intervention of CANTASTIM in other points in the cytokine network involved in endotoxin shock cannot be excluded.