OR THE SURVIVAL OF MULTICELLULAR
well-controlled cooperation of cell proliferation
and differentiation as well as death and elimina-
tion of unnecessary, useless, or even harmful cells
is essential. In bone marrow cell proliferation is
regulated by a network of cytokines such as inter-
leukin 3 or interleukin 5 and numerous growth
factors that specifically act on cells of distinct dif-
ferentiation stages and lineage relationships.
the contrary, the elimination of hematopoietic
cells is strictly controlled by programmed cell
death. In contrast to cell death by necrosis, which
induces an inflammatory response,
cell death is triggered by an energy-consuming
process that is not associated with inflammation.
Peritonitis-induced sepsis and septic shock are
characterized by the extremely high demand of
immunocompetent cells, resulting from bacterial
infection in the abdomen. Sepsis and septic shock
are important clinical problems, representing the
most common cause of death in surgical intensive
A characteristic feature of the early
phase of sepsis is a hypermetabolic state with
increased cell turnover.
Proliferation of B-cell
clones in response to cognate antigen is one of the
are mobilized from the bone marrow as a first line
of unspecific immune defense.
However, there is
also an increased consumption of immunocompe-
tent cells in the septic state by phagocytosis, anti-
gen-antibody interactions, development of pus,
disseminated intravascular coagulation, and surgi-
cal blood loss.
As a response to the increased
demand of blood cells in sepsis, leukocytes are
recruited from the bone marrow with the frequent
appearance of immature band neutrophils in the
periphery. In the current study the effects of peri-
tonitis-induced sepsis on the critical balance of
proliferation, differentiation, and apoptosis of
bone marrow cells were investigated with use of a
recently established mouse model (colon ascen-
dens stent peritonitis [CASP]) in which abdominal
sepsis is induced by insertion of a stent in the
Impact of experimental peritonitis on
bone marrow cell function
Winfried Barthlen, Nikolaus Zantl, Klaus Pfeffer, Claus-Dieter Heidecke, Bernhard Holzmann, and
Joseph Stadler, Munich, Germany
Background. The effects of abdominal sepsis on the regulation of cell turnover in bone marrow and on
the function of hematopoietic stem cells were investigated.
Methods. In a new mouse model of abdominal sepsis (colon ascendens stent peritonitis [CASP]) the pro-
liferation, apoptosis, and colony-forming capacity of bone marrow cells were determined.
Results. Both experimental peritonitis and sham surgery increased proliferation of bone marrow cells sig-
nificantly (P < .01). Incubation with granulocyte-macrophage colony-stimulating factor but not granulo-
cyte colony-stimulating factor further augmented proliferation of bone marrow cells from septic mice. In
contrast to cell proliferation, bone marrow cell apoptosis was significantly (P < .001) increased in
response to CASP but not to sham surgery. CASP surgery and treatment of normal bone marrow cells
with lipopolysaccharide, tumor necrosis factor-
, interleukin 1
, and interferon gamma increased the
number of apoptotic cells to a similar extent. Stem cell assays revealed that during the late phase of peri-
tonitis the colony formation by granulocytic-monocytic precursors was increased, whereas mature ery-
throid colony-forming cells were suppressed. Incubation of normal bone marrow cells with lipopolysaccha-
ride and cytokines showed similar effects.
Conclusions. These results reveal differential effects of experimental peritonitis on various hematopoietic
lineages and suggest a potential role of inflammatory mediators for the dysregulation of bone marrow
cell function during abdominal sepsis. (Surgery 1999;126:41-7.)
From the Department of Surgery and the Institute of Medical Microbiology, Immunology, and Hygiene,
Technical University of Munich, Klinikum rechts der Isar, Munich, Germany
Accepted Apr 3, 1999.
Supported by grant No. Si-208/5-1 from the Deutsche
Reprint requests: Winfried Barthlen, Department of Pediatric
Surgery, University Hospital of Tübingen, Hoppe-Seyler-Str 3,
Copyright © 1999 by Mosby, Inc.
0039-6060/99/$8.00 + 0 11/56/99060