POLYMICROBIAL SEPSIS BUT NOT LOW-DOSE ENDOTOXIN INFUSION CAUSES DECREASED SPLENOCYTE IL-2 IFN-GAMMA RELEASE WHILE INCREASING IL-4/IL-10 PRODUCTION/

Although studies indicate that polymicrobial sepsis produces marked de pression in lymphocyte functions, it remains unclear whether this dysf unction is due to the chronic exposure of immune cells to endotoxin (E TX; a product of the gram-negative bacterial cell wall) at levels typi cally encountered in the septic state. The aim of this study, therefor e, was to determine whether the changes in lymphokine release seen dur ing polymicrobial sepsis are comparable to those observed with chronic ETX infusion. To assess this, splenocytes were harvested from C3H/HeN mice (ETX-sensitive) at 1 or 24 hr following cecal ligation and punct ure (CLP; to induce polymicrobial sepsis), Sham CLP (Sham), or laparot omy followed by peritoneal implantation of a mini-osmotic pump which d elivered either saline vehicle (Sal-pump) or ETX (ETX-pump; 0.025 mu g lipopoly-saccharide/25 g body wt/24 hr). Splenocytes were then stimul ated with concanavalin A (2.5 mu g/ml/48 hr) and their capacity to rel ease interleukin (IL)-2, interferon (IFN)-gamma, IL-4, and IL-10 was d etermined by bioassay or ELISA. The results indicated that there were no changes in lymphokine release capacity at I hr after CLP or ETX-pum p implantation. However, prolonged sepsis (i.e., at 24 hr) caused a ma rked suppression of IL-2 and IFN-gamma release (immune-enhancing lymph okines characteristic of T(h)1-cells), while enhancing the release of immunosuppressive T(h)2-cell products IL-4 and IL-10. Chronic exposure to ETX at a level comparable to that seen in CLP caused no depression in lymphokine (IL-2/IFN-gamma) release. This implies that a bacterial component other than ETX mediates the differential alterations observ ed in lymphokine release during prolonged polymicrobial sepsis. (C) 19 94 Academic Press, Inc.