Cancer causes increased mortality and is associated with altered apoptosis in murine sepsis.
OBJECTIVE
Whereas most septic patients have an underlying comorbidity, most animal models of sepsis use mice that were healthy before the onset of infection. Malignancy is the most common comorbidity associated with sepsis. The purpose of this study was to determine whether mice with cancer have a different response to sepsis than healthy animals.


METHODS
Prospective, randomized controlled study.


METHODS
Animal laboratory in a university medical center.


METHODS
C57Bl/6 mice.


METHODS
Animals received a subcutaneous injection of either 250,000 cells of the transplantable pancreatic adenocarcinoma cell line Pan02 (cancer) or phosphate-buffered saline (healthy). Three weeks later, mice given Pan02 cells had reproducible, nonmetastatic tumors. Both groups of mice then underwent intratracheal injection of either Pseudomonas aeruginosa (septic) or 0.9% NaCl (sham). Animals were killed 24 hrs postoperatively or followed-up 7 days for survival.


RESULTS
Mice with cancer and healthy mice appeared similar when subjected to sham operation, although cancer animals had lower levels of T- and B-lymphocyte apoptosis. Septic mice with cancer had increased mortality compared to previously healthy septic mice subjected to the identical injury (52% vs. 28%; p = .04). This was associated with increased bacteremia but no difference in local pulmonary infection. Septic mice with cancer also had increased intestinal epithelial apoptosis. Although sepsis induced an increase in T- and B-lymphocyte apoptosis in all animals, septic mice with cancer had decreased T- and B-lymphocyte apoptosis compared to previously healthy septic mice. Serum and pulmonary cytokines, lung histology, complete blood counts, and intestinal proliferation were similar between septic mice with cancer and previously healthy septic mice.


CONCLUSIONS
When subjected to the same septic insult, mice with cancer have increased mortality compared to previously healthy animals. Decreased systemic bacterial clearance and alterations in intestinal epithelial and lymphocyte apoptosis may help explain this differential response.
Fox
Amy C
AC
Departments of Surgery, Washington University School of Medicine, St Louis, MO, USA.
Robertson
Charles M
CM
Belt
Brian
B
Clark
Andrew T
AT
Chang
Katherine C
KC
Leathersich
Ann M
AM
Dominguez
Jessica A
JA
Perrone
Erin E
EE
Dunne
W Michael
WM
Hotchkiss
Richard S
RS
Buchman
Timothy G
TG
Linehan
David C
DC
Coopersmith
Craig M
CM
D000230:Adenocarcinoma / Q000401:mortality* / Q000473:pathology*; D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D001402:B-Lymphocytes / Q000473:pathology; D016470:Bacteremia / Q000401:mortality* / Q000473:pathology*; D045744:Cell Line, Tumor; D015897:Comorbidity; D004195:Disease Models, Animal; D007413:Intestinal Mucosa / Q000473:pathology; D008168:Lung / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D009368:Neoplasm Transplantation; D010190:Pancreatic Neoplasms / Q000401:mortality* / Q000473:pathology*; D011552:Pseudomonas Infections / Q000401:mortality / Q000473:pathology*; D011550:Pseudomonas aeruginosa; D018805:Sepsis / Q000401:mortality* / Q000473:pathology*; D013601:T-Lymphocytes / Q000473:pathology