B. N. Jacobs1, M. J. Delano1 1University Of Michigan,General Surgery,Ann Arbor, MI, USA
Introduction:
Sepsis is the leading cause of death in the critically ill.. Poor outcomes are attributed to immune dysregulation and susceptibility to nosocomial infection. Sepsis produces a TH1 to TH2 immune shift associated with poor outcomes. The specific impact of theTH1 to TH2 shift on immune function is unknown. We investigate the timing and impact of the TH1 to TH2 response on immune function.
Methods:
C57Bl/6 mice underwent cecal ligation and puncture (LD10) or sham procedure. Plasma cytokine measurements were taken over 10 days. On days 3 and 7 post sepsis, baseline antibody production was measured. Mice were immunized with NP-KLH. T-cell dependent B-cell class-switching and antigen-specific immunoglobulin production were measured. On day 3 or 7 TH1 and TH2 functions were tested by inoculating mice with a lethal dose of L. monocytogens or P. aeruginosa. Spleen and liver were evaluated for bacterial colonization. At days 3 and 7 post sepsis mice were euthanized, and spleen and bone marrow monocyte number and function assessed.
Results:
TH1 (IFN, GM-CSF, TNF, IL-2, IL-12p40, IL-3, IL12p70) and TH2 (IL-4, GM-CSF, IL-5, IL-10, IL-6, IL-13) cytokines were elevated in a biphasic pattern. T-cell dependent B-cell class-switching and antigen-specific production showed equivalent increases in both TH1 and TH2 antibody subtypes. Septic mice eradicated and survived lethal Listeriosis at both 3 and 7 days post sepsis while sham and control mice did not. Mice treated with lethal Pseudomonas on day 3 post sepsis died, whereas mice treated on day 7 preferentially survived. After sepsis mice were able to eradicate Listeria from the spleen and bone marrow, but not Pseudomonas form the lung. Monocyte phagocytic function was greatly increased in CLP vs sham mice.
Conclusion:
The data indicate that sepsis produces both functional TH1 and TH2 immune responses. There is a transient deficit in the TH2 immunity early after sepsis that may contribute to nosocomial infection development.