Kupffer cell blockade increases mortality during intra-abdominal sepsis despite improving systemic immunity

Abstract

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.