Experimental studies on bacterial product cantastim derived from Pseudomonas aeruginosa. VI. Protection in tolerant mice.
Endotoxin tolerance is defined as a hyporesponsiveness state to a second stimulation with lipopolysaccharide (LPS). This refractory state is primarily associated with an attenuated cytokine production. Whether this down-regulation of cytokine production results in an increased susceptibility to infection remains a matter of controversy. The aim of this study was to investigate the resistance of tolerant mice to a subsequent bacterial infection and the role of bacterial immunomodulator CANTASTIM (CS) in this experimental model. We have shown that the LPS-tolerant mice (intraperitoneally inoculated with LPS Salmonella typhimurium 10 microg/mouse, daily for two days) were protected against a challenge with Pseudomonas aeruginosa (LD 100) administered 24 h later. On the contrary, when the animals were challenged 1 h after the last LPS injection, they did not survive. However if these animals were pre-treated with CS 3 days before LPS treatment, they became resistant to a subsequent bacterial challenge. More interestingly, if the treatment with LPS was substituted with CS (same schedule, route of administration and doses) there was a significant increase in the survival of mice challenged with Pseudomonas aeruginosa after either 1 h or 24 h. In this case, the increase in the rate of survival was correlated with an enhanced production of IL-10 in the peritoneal cavities of CS treated mice as compared to LPS treated mice.
Caraş
Iuliana
I
National Institute of Research--Development for Microbiology and Immunology "Cantacuzino", Immunomodulators Group, Bucharest, Romania.
Sălăgeanu
Aurora
A
D000818:Animals; D016207:Cytokines / Q000378:metabolism; D008070:Lipopolysaccharides / Q000008:administration & dosage / Q000276:immunology*; D017737:Macrophages, Peritoneal / Q000276:immunology / Q000382:microbiology; D051379:Mice; D010743:Phospholipids; D011552:Pseudomonas Infections / Q000276:immunology* / Q000382:microbiology / Q000401:mortality / Q000517:prevention & control; D011550:Pseudomonas aeruginosa / Q000276:immunology / Q000378:metabolism* / Q000472:pathogenicity; D016896:Treatment Outcome
D016207:Cytokines; D008070:Lipopolysaccharides; D010743:Phospholipids; C049675:cantastim