Kupffer cell blockade increases mortality during intra-abdominal sepsis despite improving systemic immunity
M. P. Callery, T. Kamei and M. W. Flye
Department of Surgery, Washington University School of Medicine, St. Louis, MO 63110.
The effect of Kupffer cell (KC) blockade on systemic immunity during
intra-abdominal sepsis was evaluated. Gadolinium chloride, a rare earth
metal, reduced KC phagocytosis by 75% when it was given to BALB/c mice for
2 days. Thereafter, control mice and mice with KC blockade underwent either
a sham operation or a cecal ligation and puncture. As indicators of
systemic cell-mediated immunity, delayed-type hypersensitivity responses to
soluble antigen and cellular alloantigen were measured 24 hours after the
abdominal operations. The activation of KCs was assessed by their in vitro
interleukin 1 production. Control septic mice were profoundly
immunosuppressed and demonstrated marked KC activation. Septic mice with KC
blockade, however, demonstrated less systemic immune hyporesponsiveness and
significantly reduced KC activation, but died more rapidly. We concluded
that despite apparent improvement in systemic immunity by KC blockade
during intra-abdominal sepsis, the resulting impairment in functional
phagocytic integrity predisposes to significantly higher mortality.
