Interleukin-10 gene transfer improves the survival rate of mice inoculated with Escherichia coli.
OBJECTIVE
To determine whether administration of recombinant adenovirus vectors encoding the interleukin (IL)-10 protein (AxCAmIL-10) decreases the mortality of septic mice.


METHODS
Prospective, randomized, controlled study.


METHODS
University research laboratory.


METHODS
Adult male C57B/6 mice.


METHODS
Untreated mice and those injected intraperitoneally with 1 x 10(9) pfu of AxCAmIL-10 were used as control 1 and 2, respectively. Double-capsules without Escherichia coli were intraperitoneally embedded in another group (control 3). Mice embedded with capsules containing E. coli were divided into the following groups: simultaneous administration of 0.5 mL of saline (group 1), and administration of AxCAmIL-10 3 hrs before embedding (group 2) or 1 hr after embedding (group 3). Histopathologic changes together with expression concentrations of IL-10 and tumor necrosis factor (TNF) in various organs and plasma were examined 18 hrs after each treatment. Observation periods were 5-8 days. Survival rates were compared between these groups.


RESULTS
The plasma IL-10 concentrations were increased in control 2, group 2, and group 3 but not in control 1, control 3, or group 1, indicating successful adenovirus gene transfer. Plasma TNF values were significantly reduced in groups 2 and 3 as compared with group 1, with no significant differences in endotoxin concentrations. Survival rates were significantly better in groups 2 and 3 than in group 1 (p < .05).


CONCLUSIONS
These findings suggested that IL-10 has a favorable effect on survival of septic mice via inhibition of TNF production or endotoxin stimulation.
Takakuwa
T
T
Critical Care and Emergency Center, Iwate Medical School, Graduate School of Medicine, Osaka University, Suita-City, Japan.
Endo
S
S
Shirakura
Y
Y
Yokoyama
M
M
Tamatani
M
M
Tohyama
M
M
Aozasa
K
K
Inada
K
K
D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D004926:Escherichia coli / Q000235:genetics*; D018014:Gene Transfer Techniques; D016753:Interleukin-10 / Q000097:blood* / Q000235:genetics*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D011446:Prospective Studies; D011897:Random Allocation; D018805:Sepsis / Q000097:blood* / Q000401:mortality*; D015996:Survival Rate; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10