Kupffer cell modulation of the systemic immune response
J. C. Marshall, C. Lee, J. L. Meakins, R. P. Michel and N. V. Christou
The effects of global hepatic injury and of Kupffer cell activation on
systemic immunity were studied in an in vivo rat model, using the diameters
of the delayed-type hypersensitivity (DTH) response to keyhole limpet
hemocyanin and of a subcutaneous Staphylococcus aureus abscess as measures
of systemic immunoresponsiveness. Hepatic injury with carbon tetrachloride
resulted in significant suppression of the DTH score (5.5 +/- 0.7 vs 8.8
+/- 0.8 mm). Kupffer cell activation with intraportal Escherichia coli was
likewise suppressive (DTH score, 4.4 +/- 0.5 vs 6.1 +/- 0.4 mm for animals
receiving systemic E coli); the magnitude of this suppression correlated
with the numbers of organisms extracted by the liver. Conversely, Kupffer
cell ablation with carrageenan lessened the immunosuppressive effects of
anesthesia and surgery (DTH score, 8.5 +/- 0.9 vs 6.8 +/- 0.6 mm for
controls; S aureus abscess, 4.1 +/- 0.4 vs 5.7 +/- 0.4 mm for controls).
These results indicate that Kupffer cells can modulate the systemic immune
response and suggest that gram-negative portal bacteremia with resultant
Kupffer cell activation may contribute to the immunologic derangements
characteristic of trauma and critical surgical illness.
