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Departments of
*
Pathology and
Internal Medicine, Division of Pulmonary and Critical Care, University of Michigan Medical School, Ann Arbor, MI 48109
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Abstract |
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 Top Abstract IntroductionMaterials and MethodsResultsDiscussionReferences |
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and the proinflammatory cytokine TNF-.
Collectively, these results suggest that endogenous IL-13 protected
mice from CLP-induced lethality by modulating inflammatory responses
via suppression of overzealous production of inflammatory
cytokines/chemokines in tissues. |
Introduction |
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TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
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IL-13, like IL-10, has been shown to exert potent
anti-inflammatory properties (6, 7). In vitro, IL-13
modulates monocyte-derived TNF-, IL-1, and IL-8 while stimulating
the production of IL-1 receptor antagonist and increasing the
expression and release of the IL-1 type II decoy receptor
(6, 7, 8, 9). Recent experiments in a murine model of
endotoxemia in which exogenous IL-13 treatment protected mice from
lethal endotoxemia by reducing systemic production of TNF- confirmed
the anti-inflammatory properties of IL-13 in vivo
(10, 11, 12). However, no increase in IL-13 levels has been
detected in plasma of patients with sepsis or endotoxemic volunteers
(13). Therefore, unlike with known immune-regulating
cytokines like IL-10, it is not known whether endogenous IL-13 actually
functions as a host defense mechanism during the evolution of sepsis.
To our knowledge, there is no report describing the in vivo functional
role of endogenous IL-13 in human sepsis or in experimental models of
endotoxemia and sepsis.
The aim of the present study was to elucidate the functional role of endogenous IL-13 in experimental sepsis. For this purpose, we employed a murine model of septic peritonitis induced by cecal ligation and puncture (CLP),3 which possesses a number of the hallmarks of clinical sepsis with peritonitis associated with postsurgical or accidental trauma (14). Using this model, we have found that IL-13 is expressed rapidly post-CLP in tissues including liver, lung, and kidney. Interestingly, no increased level of this mediator was found in either the peritoneal fluid or serum. The contribution of IL-13 to the evolving septic response was assessed by passive immunization with anti-IL-13 Abs. These studies have demonstrated that IL-13 is an important cytokine that is involved in regulating organ-specific inflammation by controlling the production of tissue levels of specific cytokines and chemokines.
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Materials and Methods |
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TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
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Female CD-1 mice (6–8 wk of age) were purchased from The Jackson Laboratory (Bar Harbor, ME) and housed for at least 7 days before manipulations. The mice were subjected to CLP surgery, as described previously (5, 14). In brief, the mice were anesthetized with i.p. injection of ketamine HCl (Vetamine, Mallinckrodt Veterinary, Mundelein, IL) before inhaled methoxyflurane (Metafane, Mallinckrodt Veterinary). Under sterile conditions, the cecum was exposed through a 1- to 2-cm incision of the lower left abdomen, it was ligated with a 3-0 silk suture below the ileocecal valve, and then it was punctured through and through once with a 21-gauge needle. The cecum was replaced in the peritoneum and the abdomen was closed with surgical staples. The mice were injected with 1 ml of saline s.c. for fluid resuscitation and were placed on a heating pad until they recovered from anesthesia.
Neutralization of IL-13
Passive neutralization of IL-13 was conducted by i.p. injection
of 0.5 ml of anti-murine IL-13 antiserum twice, 2 h before CLP
and 2 days after CLP. The volume of antiserum was considered to be
sufficient to neutralize systemic endogenous IL-13 in that the
biological half-life of the Ab was 
36 h (C. M. Hogaboam,
unpublished observation). Anti-murine IL-13 polyclonal Abs were raised
by immunizing New Zealand White rabbits with recombinant murine IL-13
(R&D Systems, Minneapolis, MN). Polyclonal Abs were titered by direct
ELISA and these Abs recognized murine IL-13 at a dilution of 1 x
10-7. The Abs completely blocked the ability of
IL-13 to inhibit the production of TNF-, macrophage inflammatory
protein (MIP)-2, and MIP-1 by LPS-stimulated macrophages in vitro
and did not cross-react with other murine recombinant cytokines and
chemokines. As a control, preimmune rabbit serum was used. The
endotoxin content in both anti-IL-13 antiserum and control serum
was below detection level (<0.05 EU/ml PYROGENT; BioWhittaker,
Walkersville, MD).
Experimental protocol
In the first set of experiments, mice were monitored for 7 days after CLP to determine the mortality rate induced with CLP. In the next set of experiments, the CLP mice were anesthetized at specific time points, euthanized, and bled. The peritoneal cavities were washed with 2 ml of sterile saline, and the lavage fluids were collected. After taking a 10-µl aliquot of lavage fluids for assessment of bacteria colony-forming units, the fluids were centrifuged at 6000 x g for 1 min at 4°C, and cell-free peritoneal fluids were stored at -20°C. Cell pellets were resuspended in saline, and the cell numbers were counted in a hemocytometer; in addition, differential cell analysis was made after Diff-Quik staining of the smear slides (Dade, Düdingen, Switzerland). The liver, lung, and kidney were excised, weighed, frozen in liquid nitrogen, and stored at -20°C for subsequent analyses.
Determination of CFU
Ten microliters of peritoneal lavage fluids and peripheral blood from each mouse were placed on ice and were serially diluted with sterile saline. Ten microliters of each dilution was plated on thymic-shared Ag blood agar plates (Difco, Detroit, MI) and incubated overnight at 37°C after which the number of colonies was counted. Data were expressed as CFU/10 µl.
Clinical chemistry
Serum levels of aspartate transaminase (AST), alanine transaminase (ALT), blood urea nitrogen (BUN), and creatinine were measured by Clinical Pathology at the University of Michigan Medical School (Ann Arbor, MI) using standardized techniques.
Measurement of cytokines and myeloperoxidase (MPO)
Murine IL-13 was quantitated using a standard method of sandwich
ELISA. In brief, microtiter plates (Nunc Immuno-Plate I 96-F, Nunc,
Roskilde, Denmark) were coated with 50 µl of affinity-purified
anti-murine IL-13 IgG (1 µg/ml) in coating buffer (0.6 M NaCl,
0.26 M H3BO4, and 0.08 M
NaOH (pH 9.6)). Detection and processing were made by using
biotinylated rabbit anti-murine IL-13 IgG (3.5 µg/ml),
streptavidin-peroxidase conjugate (Bio-Rad, Richmond, CA), and
chromogen substrate (Bio-Rad). The protein concentrations of murine
TNF-, IL-10, MIP-1, MIP-2, KC, and monocyte chemoattractant
protein (MCP)-1 were measured by specific ELISAs, as previously
described in detail (5, 15). The ELISAs employed in this
study did not cross-react with other murine cytokines and consistently
detected murine cytokine concentrations above 25 pg/ml.
MPO in tissue extracts was measured by using an ELISA kit (Calbiochem-Novabiochem, San Diego, CA) according to the manufacturer’s instruction. The lower detection limit was 1.6 ng/ml.
Preparation of tissue extracts
Excised tissues (0.1 g) were placed in 1 ml of homogenization buffer (500 mM NaCl and 50 mM HEPES (pH 7.4) containing 0.1% Triton X-100, 0.5 µg/ml leupeptin, 1 mM PMSF, and 0.02% NaN3) and homogenized with a Tissue Tearor (model 985-370; Biospec Products, Racine, WI). The homogenates subsequently received freeze/thaw extraction once for ELISA and three times for MPO assay. The homogenates were centrifuged at 6000 x g for 20 min at 4°C, and the cleared supernatants were used for measurement of cytokines or MPO.
Immunohistochemistry
Liver, lung, and kidney were excised at 24 h after CLP surgery, fixed in 4% paraformaldehyde, dehydrated, and embedded in paraffin, and 4-µm thin sections were prepared. Alveolar macrophages, harvested at 24 h after CLP, were sedimented at 1 x g onto BSA-coated glass slides, air-dried, and fixed in 100% ethanol for 10 min. Immunostaining was conducted using Dako EnVision System (Dako, Carpinteria, CA) according to the manufacturer’s instructions. In brief, endogenous peroxidase activity was blocked with 0.3% H2O2 in methanol, and the sections and smear slides were incubated for 30 min with 1000x diluted anti-murine IL-13 antiserum at room temperature. The specimens were rinsed and then incubated for 30 min with peroxidase-labeled polymer (Dako) at room temperature. As a chromogen, diaminobenzidine (Dako) was used. Counterstaining was performed with hematoxylin. Diluted preimmune serum (1000x) was used as a control.
RT-PCR
The tissues were homogenized in Trizol Reagent (Life
Technologies, Grand Island, NY), and total RNA was isolated according
to the manufacturer’s instructions. First-strand cDNA was constructed
from 2 µg of total RNA with oligo (dT)12–18 as
primers, and the first-strand cDNAs were then amplified by each PCR in
the presence of Taq polymerase (Life Technologies) and
specific primers. The primers were designed to amplify murine
cytokines/chemokines referred to the cDNA sequence from the
National Center for Biotechnology Information database. The
primers are as follows. MIP-2: sense, 5'-GCTGGCCACCAACCACCAGG-3';
anti-sense, 5'-AGCGAGGCACATCAGGTACG-3'. KC: sense,
5'-TGAGCTGCGCTGTCAGTGCCT-3'; antisense,
AGAAGCCAGCGTTCACCAGA-3'.MIP-1: sense,
5'-GCCCTTGCTGTTCTTCTCTGT-3'; antisense, 5'-GGCAATCAGTTCCAGGTCAGT-3'.
TNF-: sense, 5'-CTTCCAGAA CTCCAGGCGGT-3'; antisense,
5'-GAGGAGGTTGACTTTCTCCT-3'. GAPDH: sense,
5'-GGTGAAGGTCGGTGTCAACGGATTT-3'; anti-sense,
5'-GATGCCAAAGTTGTCATGGATGACC-3'. The PCR reaction was conducted at 35
cycles of 94°C for 1 min, 55°C for 1 min, and 72°C for 1
min. Twenty microliters of each PCR product was subjected to
electrophoresis on a 2% agarose gel in the presence of ethidium
bromide and photographed, then the images were digitized, and the band
densities were measured with NIH Image. Results are expressed as a
ratio of each PCR product/GAPDH band density, and this represents
semiquantitative analysis.
Statistics
Statistical significance was determined by ANOVA with p values <0.05. In case of survival curve and CFU count, the data were analyzed by the log-rank test and Mann-Whitney test, respectively. A p value <0.05 was regarded as statistically significant. All data were expressed as the mean ± SD.
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Results |
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TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
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In initial investigations, we first measured the local and
systemic levels of IL-13 during the evolution of CLP-induced sepsis.
The expression of IL-13 in the liver, lung, and kidney was
significantly increased after CLP (Fig. 1
); however, there was not a significant
increase in the levels of IL-13 in the peritoneal fluid or serum after
CLP (data not shown). IL-13 levels in liver and kidney reached a peak
at 4 and 8 h post-CLP, respectively, and remained elevated at
48 h, whereas IL-13 levels in the lung gradually increased with
time (Fig. 1). The peak levels of IL-13 in liver, lung, and kidney were
3.2-, 5.0-, and 6.0-fold higher, respectively, than those in normal
tissue. To identify the cells expressing IL-13 in tissues,
immunohistochemical staining was performed. As shown in Fig. 2, Kupffer cells in the liver and
epithelial cells in the urinary tubules stained positive in tissue
sections obtained at 24 h post-CLP (Fig. 2, A and
E). IL-13-positive cells in lung tissue section could not be
determined, but alveolar macrophages collected by lavage at 24 h
after CLP were positively stained (Fig. 2C). Control Abs
were not reactive, indicating the specificity of the staining (Fig. 2, B, D, and F). The above data indicate
that IL-13 levels were augmented only in tissues during the evolution
of CLP-induced peritonitis.
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To examine the involvement of IL-13 in CLP-induced peritonitis
leading to lethality, either anti-IL-13 Abs or control Abs were
i.p. injected 2 h before CLP surgery and 2 days after CLP, and the
survival rates were monitored. As shown in Fig. 3, neutralization of IL-13 significantly
decreased the survival of mice after CLP. The detrimental effects were
most apparent at 48 h, when the mortality rate in control mice was
30% (9/30 mice), whereas a striking 64% mortality rate (18/28 mice)
was observed in mice treated with anti-IL-13 Abs (Fig. 3). On day
7, 53% of control mice (16/30 mice) survived compared with 14% of
anti-IL-13 Ab-treated mice (4/28 mice).
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), suggesting that either
endogenous IL-4 does not function in the same manner as IL-13 or IL-4
is not produced in significant quantities in this model. In fact, no
significant increases were found in the level of IL-4 in the
peritoneum, serum, or tissues after CLP. The above results do clearly
indicate a protective role of endogenous IL-13 but not IL-4 in
CLP-induced lethality. IL-13 blockade does not affect the local inflammation induced by CLP
To identify the mechanisms whereby IL-13 exerted a protective role
in CLP, experiments were conducted to assess the local effects of
anti-IL-13 Abs. Blockade of IL-13 resulted in no change in the
numbers of either infiltrating neutrophils or macrophages in the
peritoneum at any time point after CLP, compared with control (data not
shown). Production of chemokines that attract leukocytes in the
peritoneum, which include MIP-2, KC, MIP-1, and MCP-1, increased
after CLP, but these levels were unchanged by anti-IL-13 Abs,
compared with control (data not shown). Because activated leukocytes
phagocytose and eliminate bacteria (18), we determined the
phagocytic index of the peritoneal leukocytes by assessing the bacteria
load in the peritoneum after CLP. At 24 h after CLP, the recovery
of bacteria from the peritoneum was found in 9/10 mice treated with
control Abs, and the mean CFU was 1.2 x
106/10 µl of peritoneal fluids. At this same
time point, similar levels of viable bacteria were recovered from the
peritoneum of mice that received anti-IL-13 Abs (9/9 mice; mean
CFU = 0.9 x 106/10 µl, not
significant compared with control). Thus, it appears that endogenous
IL-13 does not play a role in regulating the phagocytic and
bactericidal activity of the infiltrating leukocytes.
IL-13 blockade augments systemic tissue inflammation and tissue injury induced by CLP
Next, experiments were conducted to assess the systemic effects of
anti-IL-13 Abs. To examine systemic inflammation, we measured the
level of MPO in tissues as an indirect means to determine the
recruitment of neutrophils. Neutralization of IL-13 resulted in a
significant increase in MPO levels in the liver and kidney compared
with control (Fig. 4). MPO levels in the
lung were also increased by 30% after anti-IL-13 treatment,
although the difference was not statistically significant (control vs
anti-IL-13 Abs; 29.5 ± 4.2 ng/0.1 g lung (n =
9) vs 39.1 ± 3.8 ng/0.1 g lung (n = 9);
p = 0.106; Fig. 4). Treatment with anti-IL-13 Abs
also significantly increased serum levels of AST, ALT, BUN, and
creatinine compared with control (Fig. 5). The data indicate that endogenous
IL-13 modulates systemic tissue inflammation and tissue dysfunction
evolved by CLP.
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, and TNF- in tissues
To elucidate the mechanisms whereby anti-IL-13 treatment
increased the tissue inflammation during the evolution of CLP, the
levels of chemokines known to attract neutrophils, which include MIP-2,
KC, and MIP-1, were next examined after anti-IL-13 treatment.
The levels of these chemokines increased after CLP and peaked at 8–24
h after CLP (data not shown). Neutralization of IL-13 resulted in
significant increases in the level of CXC chemokines MIP-2 and KC in
liver, lung, and kidney compared with controls. As shown in Fig. 6, anti-IL-13 treatment markedly
increased the levels of MIP-2 and KC in tissues at 8 h after CLP.
Twenty-four hours after CLP, the levels of MIP-2 in the lung and kidney
and the level of KC in the kidney were still higher than those in
control (Fig. 6A). The mRNA expressions for MIP-2 and KC in
all tissues examined were up-regulated by anti-IL-13 Abs compared
with control (Fig. 6, B and C). The level of CC
chemokine MIP-1 in the lung remained elevated after 24 h for
anti-IL-13-treated mice but decreased at 24 h in control mice
compared with the level at 8 h (Fig. 7A). MIP-1 in the kidney
was increased at 8 h after the treatment with anti-IL-13 Abs,
and the significant increase was still found at 24 h after CLP
(Fig. 7A). We also assessed the production of
proinflammatory cytokine TNF-, which is known to be involved in the
pathogenesis of sepsis (3), in our model of sepsis. The
levels of TNF- in tissues after CLP increased with time for up to
24 h (data not shown). Neutralization of IL-13 significantly
increased the level of TNF- in the liver (24 h) and kidney (8 and
24 h) but not in the lung, compared with control (Fig. 7A). The mRNA expressions for MIP-1 in the lung (18 h
after CLP) and kidney (3 and 18 h) and for TNF- in the liver
(18 h) and kidney (3 and 18 h) were up-regulated by anti-IL-13
Abs (Fig. 7, B and C). Thus, the in vivo
neutralization of IL-13 increased the gene expression and protein
production of neutrophil-activating chemokines and proinflammatory
cytokine (TNF-) in specific tissues.
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Discussion |
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TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
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Sepsis induced by CLP initiates in the peritoneum, where the local
inflammatory response is essential for eliminating invading pathogens
from the infectious foci. Previously, IL-13 has been shown to inhibit
the production of inflammatory cytokines/chemokines in vitro and in
vivo (6, 7, 10, 11, 12). Administration of IL-13 reduced the
recruitment of leukocytes in a model of chronic, Ag-induced guinea pig
lung inflammation (21). In contrast, the neutralization of
IL-13 in IgG immune complex-induced lung inflammation enhanced
leukocyte infiltration by altering inflammatory cytokine/chemokine
production (20). Because many inflammatory cytokines
(including chemokines) are produced in the peritoneum after CLP, we
speculated that endogenous IL-13 might directly modulate local
inflammatory reactions after this insult. However, neither leukocyte
infiltration nor bacterial load in the peritoneum after CLP was altered
after the treatment with anti-IL-13 Abs. Likewise, the production
of chemokines in the peritoneum that attracts leukocytes, which include
MIP-2, KC, MIP-1, and MCP-1, was unchanged by anti-IL-13
treatment. The findings are not surprising because no significant
increase in IL-13 was found in the peritoneum after CLP throughout the
observation periods. The data indicate that IL-13 may not be involved
in the regulation of local inflammation in the CLP model with respect
to chemokine production, leukocyte infiltration, and activation of the
leukocytes.
Sepsis is known to frequently cause severe systemic inflammation called
systemic inflammatory response syndrome, which leads to multiple organ
failure, a condition that is often fatal to the host (3, 4). Interestingly, the level of IL-13 only increased in tissues
after CLP without any increase in the level of IL-13 in the peritoneal
fluids and serum, which correlates with a recent clinical report
showing that IL-13 did not increase in the plasma of patients with
sepsis and endotoxemic volunteers (13). Although the
failure to find increased IL-13 in the serum and peritoneal fluids may
be a consequence of the presence of a soluble receptor/receptor
antagonist against IL-13, the clinical and experimental findings
suggest that endogenous IL-13 exerts a protective role by modulating
specific organ/tissue inflammation after CLP. This is likely the
mechanism underlying the protective role of endogenous IL-13 in CLP
animals in that IL-13 blockade not only augmented the intensity of the
tissue inflammation but also impaired the physiological function of
specific tissues. The modulation of tissue inflammation by endogenous
IL-13 appeared to be mediated by down-regulating chemokine
production in tissues, as shown by the fact that the mRNA and protein
levels of MIP-2, KC, and MIP-1 in specific tissues were dramatically
increased after anti-IL-13 treatment compared with control. These
chemokines are known to be responsible for various types of tissue
inflammation including sepsis (2, 3, 22, 23). Furthermore,
neutralization of IL-13 increased both the mRNA and protein levels of
TNF- in tissues in our model of sepsis. The data corresponded well
to the previous reports that showed that IL-13 inhibited TNF-
production in vitro and in vivo (6, 7, 10, 11, 12). TNF- is
known to induce the expression of many types of mediators including
chemokines, and is a powerful pathogenic mediator of tissue injury
(24, 25).
The protective role of endogenous IL-13 appeared to be independent of
another anti-inflammatory cytokine IL-4 and IL-10. No appreciable
increase in IL-4 was found during sepsis induced by CLP, and
neutralization of IL-4 had no effect on the survival of mice after CLP.
We and others demonstrated that CLP led to a rapid production of IL-10
during sepsis (5, 26) and that IL-10 blockade was
detrimental to the survival of mice after CLP, which was associated
with increased level of TNF- (26, 27), indicating that
endogenous IL-10 plays a protective role during CLP-induced sepsis.
Because IL-13 has been shown to directly inhibit macrophage IL-10
production in vitro (28) and to decrease the level of
IL-10 in lethal endotoxemia (10), we asked whether IL-13
blockade would affect the production of IL-10 in our model of sepsis.
As a result, neutralization of IL-13 failed to alter the level of IL-10
in tissues after CLP (data not shown). The data suggest that IL-13
provided a protection mechanism that is similar to but independent of
IL-10.
Although IL-13 was originally identified as a product of activated Th2 cells (29, 30), recent investigations have shown that IL-13 can be produced in vitro from many types of cells such as mast cells, basophils, NK cells, fibroblasts, dendritic cells, PBMCs, or alveolar macrophages (31, 32, 33, 34, 35, 36, 37). In CLP animals, IL-13 was immunohistochemically detected in liver Kupffer cells, lung alveolar macrophages, and kidney epithelial cells in urinary tubules. There are other possible sources of IL-13 in the lung such as mast cells, NK cells, or T cells; however, we believe that alveolar macrophages are the main cells producing IL-13 in the lungs of animals undergoing CLP.
The data obtained in this study demonstrate the beneficial effects of endogenous IL-13 in the septic peritonitis. The levels of IL-13 were increased in the liver, lung, and kidney during the evolution of CLP, and neutralization of endogenous IL-13 resulted in an enhanced expression and production of inflammatory cytokines/chemokines, augmented tissue inflammation, and induced tissue dysfunction. Thus, it appears that endogenous IL-13 protected mice from CLP-induced lethality by modulating systemic inflammatory responses via suppression of the overzealous production of tissue-specific inflammatory cytokines and chemokines.
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Acknowledgments |
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Footnotes |
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2 Address correspondence and reprint requests to Dr. Steven L. Kunkel, Department of Pathology, University of Michigan Medical School, 1301 Catherine Road, Ann Arbor, MI 48109-0602. E-mail address:
3 Abbreviations used in this paper: CLP, cecal ligation and puncture; MIP, macrophage inflammatory protein; MCP, monocyte chemoattractant protein; MPO, myeloperoxidase; AST, aspartate transaminase; ALT, alanine transaminase; BUN, blood urea nitrogen.
Received for publication August 10, 1999. Accepted for publication December 17, 1999.
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 W. Kang, H. Saito, K. Fukatsu, A. Hidemura, H. Koyama, T. Sakamoto, and K. Maekawa Effects of Tyrosine Kinase Signaling Inhibition on Survival After Cecal Ligation and Puncture in Diet-Restricted Mice JPEN J Parenter Enteral Nutr, November 1, 2001; 25(6): 291 - 298. [Abstract] [PDF]
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V. Supajatura, H. Ushio, A. Nakao, K. Okumura, C. Ra, and H. Ogawa Protective Roles of Mast Cells Against Enterobacterial Infection Are Mediated by Toll-Like Receptor 4 J. Immunol., August 15, 2001; 167(4): 2250 - 2256. [Abstract] [Full Text] [PDF]
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M. E. Sewnath, D. P. Olszyna, R. Birjmohun, F. J. W. ten Kate, D. J. Gouma, and T. van der Poll IL-10-Deficient Mice Demonstrate Multiple Organ Failure and Increased Mortality During Escherichia coli Peritonitis Despite an Accelerated Bacterial Clearance J. Immunol., May 15, 2001; 166(10): 6323 - 6331. [Abstract] [Full Text] [PDF]
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K. Blease, C. Jakubzick, J. Westwick, N. Lukacs, S. L. Kunkel, and C. M. Hogaboam Therapeutic Effect of IL-13 Immunoneutralization During Chronic Experimental Fungal Asthma J. Immunol., April 15, 2001; 166(8): 5219 - 5224. [Abstract] [Full Text] [PDF]
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A. Matsukawa, M. H. Kaplan, C. M. Hogaboam, N. W. Lukacs, and S. L. Kunkel Pivotal Role of Signal Transducer and Activator of Transcription (Stat)4 and Stat6 in the Innate Immune Response during Sepsis J. Exp. Med., March 12, 2001; 193(6): 679 - 688. [Abstract] [Full Text] [PDF]
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M. L. Steinhauser, C. M. Hogaboam, A. Matsukawa, N. W. Lukacs, R. M. Strieter, and S. L. Kunkel Chemokine C10 Promotes Disease Resolution and Survival in an Experimental Model of Bacterial Sepsis Infect. Immun., November 1, 2000; 68(11): 6108 - 6114. [Abstract] [Full Text] [PDF]
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;
34 mice), or control serum (
; 30 mice) was i.p. injected 2 h
before CLP and 2 days after CLP. The survival rates were monitored for
7 days after CLP. There is a statistically significant difference
(p < 0.01) between anti-IL-13 antiserum and
control, whereas there is no significant difference between
anti-IL-4 antiserum and control (log-rank test).
; 9 mice) was i.p. injected 2 h before CLP. At
24 h after CLP, mice were euthanized, and the liver, lung, and
kidney were resected. The tissues were extracted and the amounts of MPO
in liver, lung, and kidney were measured by ELISA. The data represent
the mean ± SD. 
, p < 0.05; 
