Purpose: To investigate
differences in cytokine/chemokine
release in response to lipoteichoic
acid (LTA) or lipopolysaccharide
(LPS) and contributing cellular
mechanisms, in order to improve
understanding of the pathogenesis of
sepsis. Methods: Levels of cytokines/chemokines
were measured in
plasma and peritoneal lavage fluid of
10-week-old male mice (C57/B16)
following intraperitoneal injection of
LTA or LPS (250 lg), and in supernatants
of murine J774.2 cells,
immortalised blood monocytes, or
isolated human monocytes treated
with LTA or LPS (0–10 lg/ml). The
role of cytokine/chemokine messenger
RNA (mRNA) stability versus
nuclear factor-kappaB (NF-jB) and
activator protein-1 (AP-1) in mediating
cytokine/chemokine release in
J774 cells was also assessed.
Results: In mice, plasma levels of
keratinocyte-derived chemokine
(KC), macrophage inflammatory
protein (MIP)-2, interleukin (IL)-10,
interferon (IFN)-c and tumour necrosis
factor-alpha (TNF-a) and
peritoneal lavage fluid levels of KC, MIP-2 and TNF-a increased signifi-
cantly 1 h after LPS. Only KC and
MIP-2 levels increased 1 h after LTA.
LPS-treated (10 lg/ml) J774 cells
released MIP-2, IL-10, IFN-c and
TNF-a but not KC (24 h), whereas
cells treated with 10 lg/ml LTA
released only MIP-2. LPS-stimulated
human monocytes released IL-10 and
IL-8 (24 h); by contrast, LTA-treated
cells released only IL-8. LPS and
LTA activated NF-jB and AP-1 in
J774 cells. The protein synthesis
inhibitor cycloheximide abolished
LPS-induced IL-10 mRNA expression
and increased LTA- and LPSinduced
mRNA for MIP-2 in J774
cells. Conclusion: LTA and LPS, at
clinically relevant concentrations,
induced differential cytokine/chemokine
release in vitro and in vivo, via
effects distal to activation of NF-jB/
AP-1 that might include chromatin
remodelling or mRNA stability.