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 depression in lymphocyte functions, it remains unclear whether this dysfunction is due to the chronic exposure of immune cells to endotoxin (ETX; a product of the gram-negative bacterial cell wall) at levels typically encountered in the septic state. The aim of this study, therefore, was to determine whether the changes in lymphokine release seen during 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 puncture (CLP; to induce polymicrobial sepsis), Sham CLP (Sham), or laparotomy followed by peritoneal implantation of a mini-osmotic pump which delivered either saline vehicle (Sal-pump) or ETX (ETX-pump; 0.025 micrograms lipopolysaccharide/25 g body wt/24 hr). Splenocytes were then stimulated with concanavalin A (2.5 micrograms/ml/48 hr) and their capacity to release interleukin (IL)-2, interferon (IFN)-gamma, IL-4, and IL-10 was determined by bioassay or ELISA. The results indicated that there were no changes in lymphokine release capacity at 1 hr after CLP or ETX-pump implantation. However, prolonged sepsis (i.e., at 24 hr) caused a marked suppression of IL-2 and IFN-gamma release (immune-enhancing lymphokines characteristic of Th1-cells), while enhancing the release of immunosuppressive Th2-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 observed in lymphokine release during prolonged polymicrobial sepsis.
Department of Surgery, Michigan State University, East Lansing 48824.
A
A
Ayala
Z K
ZK
Deol
D L
DL
Lehman
C D
CD
Herdon
I H
IH
Chaudry
D000818:Animals; D001424:Bacterial Infections / Q000378:metabolism*; D002432:Cecum; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004731:Endotoxins / Q000008:administration & dosage* / Q000494:pharmacology; D007260:Infusion Pumps; D007371:Interferon-gamma / Q000378:metabolism*; D016753:Interleukin-10 / Q000096:biosynthesis; D007376:Interleukin-2 / Q000378:metabolism; D015847:Interleukin-4 / Q000096:biosynthesis; D007378:Interleukins / Q000378:metabolism*; D008026:Ligation; D051379:Mice; D011677:Punctures; D013154:Spleen / Q000166:cytology / Q000378:metabolism*; D013997:Time Factors
D004731:Endotoxins; D007376:Interleukin-2; D007378:Interleukins; D016753:Interleukin-10; D015847:Interleukin-4; D007371:Interferon-gamma