Effect of Antiflagellar Human Monoclonal Antibody on Gut-Derived Pseudomonas aeruginosa Sepsis in Mice

Abstract

We evaluated the effect of antiflagellar human monoclonal antibody on gut-derived Pseudomonas aeruginosa sepsis. Mice were given a suspension of P. aeruginosa SP10052 in their drinking water and were simultaneously treated with ampicillin (200 mg/kg of body weight) to disrupt the normal bacterial flora. Cyclophosphamide was then administered to induce leukopenia and translocation of the P. aeruginosa that had colonized the gastrointestinal tract, thereby producing gut-derived generalized sepsis. In this model, intraperitoneal injection of 100 μg of antiflagellar human monoclonal antibody (SC-1225) per mouse for 5 consecutive days significantly (P < 0.01) increased the survival rate compared with that for mice treated with bovine serum albumin (BSA). Treatment with SC-1225 significantly reduced the average number of viable bacteria in portal blood, liver, and heart blood compared with the average number after treatment with BSA. Furthermore, the presence in serum of the inflammatory cytokines tumor necrosis factor alpha and interleukin 6 were evaluated as markers of severity of infection, and the results showed that the levels of these cytokines in mice treated with SC-1225 were significantly decreased in comparison with those in BSA-treated control mice. Although there was no significant difference in the number of bacteria that colonized the intestine, SC-1225 treatment significantly increased bacterial opsonophagocytosis by cultured peritoneal macrophages from mice with or without cyclophosphamide pretreatment. Our results indicate that antiflagellar human monoclonal antibody SC-1225 protects mice against gut-derived sepsis caused by P. aeruginosa and suggest that such an effect is due to its opsonophagocytic activity and the reduced motility of the translocated bacteria once the bacteria move from the intestine into the bloodstream.

Role of endogenous macrophage inflammatory protein‐2 in regulating fever induced by bacterial endotoxin in normal and immunosuppressed rats

“…Cyclophosphamide suppress the immune responses mediated by B lymphocytes, induces a selective and severe damage of peritoneal macrophages, stromal and reticular cells and disrupts hepatic sinusoidal endothelium 39–43 . Based on current data, it would seem unlikely that resident immune cell‐generated MIP‐2 could provide the signals that rapidly initiate and maintain the febrile response to LPS in neutropenic animals.…”

Protective effect of Lactobacillus casei strain Shirota against lethal infection with multi-drug resistant Salmonella enterica serovar Typhimurium DT104 in mice

“…Several experimental animal models of infection with antibiotic-resistant pathogens have been reported: infection of mice with vancomycin-resistant Enterococcus during treatment with vancomycin (Donskey et al 1999) and Pseudomonas aeruginosa infection during treatment with ampicillin (Matsumoto et al 1999). In both models, pathogens highly resistant to the antibiotic administered were used to induce reproducible opportunistic infections resulting from colonization at high population levels in the intestines during treatment of mice with the antibiotic.…”

“…Several experimental animal models of infection with antibiotic‐resistant pathogens have been reported: infection of mice with vancomycin‐resistant Enterococcus during treatment with vancomycin (Donskey et al. 1999) and Pseudomonas aeruginosa infection during treatment with ampicillin (Matsumoto et al. 1999).…”

Indole and 7‐hydroxyindole diminish Pseudomonas aeruginosa virulence

“…It is likely that P. aeruginosa encounters indole because (i) P. aeruginosa is ubiquitous (Stover et al, 2000), (ii) P. aeruginosa is found in the gut where E. coli is dominant (Wang et al, 2006) and produces gut-derived generalized sepsis (Matsumoto et al, 1999), and (iii) P. aeruginosa may also encounter E. coli outside the human body as E. coli exists outside the human host as well. Hence, it is possible Pseudomonas encounters indole and 7-hydroxyindole (7HI).…”

“…, 2000 ), (ii) P. aeruginosa is found in the gut where E. coli is dominant ( Wang et al. , 2006 ) and produces gut‐derived generalized sepsis ( Matsumoto et al. , 1999 ), and (iii) P. aeruginosa may also encounter E. coli outside the human body as E. coli exists outside the human host as well.…”