DOI: 10.1542/peds.

2007-1697
; originally published online March 17, 2008; 2008;121;e748 Pediatrics
Masahiro Noda, Kiyosu Taniguchi and Hirokazu Kimura
Kaoru Okazaki, Masatoshi Kondo, Masahiko Kato, Ryota Kakinuma, Akira Nishida,
Syndrome
Serum Cytokine and Chemokine Profiles in Neonates With Meconium Aspiration

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DOI: 10.1542/peds.2007-1697
; originally published online March 17, 2008; 2008;121;e748 Pediatrics
Masahiro Noda, Kiyosu Taniguchi and Hirokazu Kimura
Kaoru Okazaki, Masatoshi Kondo, Masahiko Kato, Ryota Kakinuma, Akira Nishida,
Syndrome
Serum Cytokine and Chemokine Profiles in Neonates With Meconium Aspiration

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ARTICLE
Serum Cytokine and Chemokine Proles in Neonates
With Meconium Aspiration Syndrome
Kaoru Okazaki, MD
a
, Masatoshi Kondo, MD
a
, Masahiko Kato, MD
b
, Ryota Kakinuma, MD
a
, Akira Nishida, MD
a
, Masahiro Noda, PhD
c
,
Kiyosu Taniguchi, MD
d
, Hirokazu Kimura, PhD
d
a
Divisions of Neonatology, Tokyo Metropolitan Hachioji Childrens Hospital, Tokyo, Japan;
b
Gunma Prefectural Institute of Public Health and Environmental Sciences,
Gunma, Japan;
c
Department of Virology III and
d
Infectious Diseases Surveillance Center, National Institute of Infectious Diseases, Tokyo, Japan
The authors have indicated they have no nancial relationships relevant to this article to disclose.
Whats Known on This Subject
We proled cytokines and chemokines in sera with meconiumaspiration syndrome. We
found that various cytokines and chemokines were signicantly elevated in meconium
aspiration syndrome, suggesting that these inammatory modulators may be associ-
ated with the pathophysiology of meconium aspiration syndrome.
What This Study Adds
The pathophysiology of meconium aspiration syndrome may be partially explained by
signicantly elevated proinammatory cytokines, chemokines, and anti-inammatory
cytokines in serum. Monoclonal antibody against proinammatory cytokines, chemo-
kines, and complement inhibitors may be applicable for meconium aspiration syn-
drome in the future.
ABSTRACT
OBJECTIVES. Various inammatory cytokines and chemokines are thought to be associ-
ated with the pathophysiology of meconium aspiration syndrome. To clarify any
such association, we compared various serum cytokine and chemokine proles in
patients with and without meconium aspiration syndrome.
PATIENTS AND METHODS. Using a highly sensitive uorescence microsphere method, 17
types of cytokines and chemokines in sera were measured in 11 neonatal patients
with meconium aspiration syndrome, 16 neonatal patients without meconium as-
piration syndrome, and 9 healthy children.
RESULTS. The concentrations of 8 types of proinammatory cytokines and chemokines
were signicantly higher in the meconium aspiration syndrome group than in
healthy controls: interleukin-1, interleukin-6, interleukin-8, granulocyte-macro-
phage colony-stimulating factor, granulocyte colony-stimulating factor, interferon-,
macrophage inammatory protein-1, and tumor necrosis factor-. Six types of
proinammatory cytokines and chemokines were signicantly higher in the meco-
nium aspiration syndrome group than in the nonmeconium aspiration syndrome
group: interleukin-6, interleukin-8, granulocyte-macrophage colony-stimulating
factor, granulocyte colony-stimulating factor, interferon-, and tumor necrosis fac-
tor-. Serum concentrations of interleukin-10 (anti-inammatory cytokine) in the
meconium aspiration syndrome group were higher than those in both the nonme-
conium aspiration syndrome group and healthy children group (P .007 and 0.001,
respectively).
CONCLUSIONS. Most types of proinammatory cytokines and chemokines in sera of
neonates with meconium aspiration syndrome were higher than those without
meconium aspiration syndrome, giving support to the suggestion that elevated levels
are associated with the pathogenesis of meconium aspiration syndrome.
M
ECONIUM IS REPORTED to be a strong inducer of severe chemical pneumonitis in neonates, resulting in meconium
aspiration syndrome (MAS).
1
The major pathogenesis of chemical pneumonitis in MAS may be responsible for the
transmigration and inltration of inammatory cells, including neutrophils and macrophages found in the alveoli, larger
airways, and the lung parenchyma, as well as bacterial pneumonia.
14
Moreover, Castellheim et al
5
reported that
meconium aspiration can lead to progressive systemic inammatory responses syndrome in newborn piglets, involving
granulocyte activation and interleukin (IL)-6 and IL-8 release. Thus, severe MAS can be life threatening because of
multiple organ failure with devastating inammation.
4,6
Previous reports demonstrated that cytokines and chemokines as immunologic responders may be strongly linked
to the various infectious lung diseases.
7,8
Although MAS is not principally an infectious disease, its pathophysiology
is similar in terms of the process of inammatory response to pneumonia caused by various pathogens.
2,3,9
Proin-
ammatory cytokines and chemokines may, therefore, be associated with the pathophysiology of MAS. Interestingly,
de Beaufort et al
10
suggested that meconium contains relatively high levels of certain types of proinammatory
www.pediatrics.org/cgi/doi/10.1542/
peds.2007-1697
doi:10.1542/peds.2007-1697
Key Words
cytokines, chemokines, MAS, neonates,
inammation, sera
Abbreviations
MASmeconium aspiration syndrome
ILinterleukin
TNFtumor necrosis factor
IFNinterferon
G-CSFgranulocyte colony-stimulating
factor
GM-CSFgranulocyte-macrophage
colony-stimulating factor
MIPmacrophage inammatory protein
BALFbronchoalveolar lavage uid
Accepted for publication Jul 31, 2007
Address correspondence to Kaoru Okazaki,
MD, Tokyo Metropolitan Hachioji Childrens
Hospital, 4-33-13 Daimachi, Hachioji, Tokyo
193-0931, Japan. E-mail: okazaki@chp.hachioji.
tokyo.jp; or Hirokazu Kimura, PhD, Infectious
Diseases Surveillance Center, National Institute
of Infectious Diseases, 4-7-1 Gakuen,
Musashimurayama, Tokyo 201-0011, Japan.
E-mail: kimhiro@nih.go.jp
PEDIATRICS (ISSNNumbers: Print, 0031-4005;
Online, 1098-4275). Copyright 2008 by the
American Academy of Pediatrics
e748 OKAZAKI et al
cytokines and chemokine, such as IL-1, IL-6, tumor
necrosis factor (TNF)-, and IL-8, directly leading to
chemical pneumonitis in MAS. Moreover, it is suggested
that leakage of aspirated meconium to the lung capillar-
ies may induce systemic inammation, such as the pro-
duction of cytokines and chemokines and the activation
of complements.
11,12
Cytokines and chemokines certainly
play pivotal roles in immunologic regulation, including
proliferation and differentiation of most types of leuko-
cytes.
13,14
The cytokines and chemokines, such as IL-1,
IL-6, IL-8, IL-10, interferon (IFN)-, and TNF- are also
involved in inammatory responses in vivo. These cyto-
kines and chemokines can activate inammatory cells,
such as neutrophils and monocytes or macrophages,
13,14
which, in turn, may release toxic substances, such as
reactive oxygen species, and toxic granules, including
proteolytic enzymes and myeloperoxidase, resulting in
cell and tissue injury.
15
However, the exact role of these
cytokines and chemokines in MAS remains unclear.
Moreover, to the best of our knowledge, this role has not
been extensively studied in the sera of neonates with
MAS. To this end, in the present study we proled 17
types of cytokines and chemokines in the sera of neo-
nates with MAS and compared them with those ob-
tained for neonates without MAS and for healthy chil-
dren.
MATERIALS ANDMETHODS
Subjects
A total of 27 neonates and 9 healthy children were the
subjects of this study. All of the neonates with MAS were
single births delivered between 37 and 41 weeks of
gestation and admitted to the NICU of Tokyo Metropol-
itan Hachioji Childrens Hospital between January 2005
and May 2006. MAS was dened as respiratory distress
in an infant born through meconium-stained amniotic
uids, roentgenographic ndings consistent with MAS,
and symptoms that could not be otherwise explained.
2
Exclusion criteria were congenital malformations, any
apparent clinical sign of infection, trauma, coagulation
disorders, and genetic disorders. Eleven neonates were
diagnosed with MAS (MAS group). The 16 neonates
without MAS (non-MAS group) were of normal vaginal
delivery with no evidence of perinatal asphyxia or meco-
nium-stained amniotic uids. The 9 healthy children
(healthy children group) ranged in age from 2 to 6 years
(3.7 1.3 years, mean SD).
To evaluate any differences in cytokines and chemo-
kines in the serum during MAS at the neonatal stage,
blood was drawn once from the umbilical artery or the
radial artery of all of the neonates diagnosed with MAS
within 6 hours after birth (3.5 1.9 hours, mean SD).
In the non-MAS group, blood samples were drawn once
from a peripheral vein within 6 hours after birth. These
samples were mainly collected to measure blood glucose
and total bilirubin. In the healthy children group, blood
samples were drawn from a peripheral vein for a preop-
erative examination of hernia repair.
Written informed consent was obtained from the par-
ents of all of the subjects for the donation of 200 L of
blood, which was used in this analysis. The study pro-
tocol was approved by the ethics committee on human
research of Tokyo Metropolitan Hachioji Childrens Hos-
pital.
Measurement of Cytokine and Chemokine Concentrations
The concentration of 17 types of cytokines and chemo-
kines in a small volume (50 L) of sera was measured
using a highly sensitive uorescence microsphere system
(Bio-Plex suspension array system, Hercules, CA).
16
The
following cytokines and chemokines were measured:
IL-1, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, IL-12,
IL-13, IL-17, granulocyte colony-stimulating factor (G-
CSF), granulocyte-macrophage colony-stimulating fac-
tor (GM-CSF), IFN-, monocyte chemoattractant pro-
tein-1, macrophage inammatory protein (MIP)-1, and
TNF-. The detectable limit of each type of cytokine or
chemokine was 0.1 to 0.3 pg/mL.
16
Oxygenation Index
The oxygenation index was calculated according to the
following formula: (mean airway pressure fraction of
inspired oxygen 100)/arterial oxygen pressure.
Statistical Analysis
Data were analyzed using SPSS software (SPSS for Win-
dows 10.0, SPSS Inc, Chicago, IL). All data are expressed
as means SEs. Apgar score is expressed as the median
and interquartile range. Statistical analysis of the cyto-
kine and chemokine concentrations was performed us-
ing the Kruskal-Wallis and Bonferroni methods. A
Mann-Whitney test was applied to compare the charac-
teristics of the patients. Statistical signicance was set at
the level of P value .05.
RESULTS
Subjects
The detailed characteristics of the subjects with and
without MAS are shown in Table 1. Signicant differ-
ences in the 1- and 5-minute Apgar scores were seen
between the MAS and non-MAS groups (P .005). No
signicant difference was found for birth weight and
gestational age. In the MAS group, none of the subjects
had positive blood or tracheal aspirate cultures, abnor-
mal C-reactive protein (0.35 mg/dL), or immunoglob-
ulin M elevation (10 mg/dL). Total leukocyte counts
ranged between 13 400 and 31 300 per L.
Among the 11 subjects in the MAS group, 8 required
assisted ventilation, 5 of which were subjects with severe
MAS, who required assisted ventilation for 48 hours.
6
Only 1 subject was complicated by persistent pulmonary
hypertension, and 7 subjects had multiple organ in-
volvement, including central nerve, hepatic, cardiac, he-
matologic, and renal injury.
17
However, there were no
cases of poor outcome including neurologic sequelae
and death in subjects with or without MAS.
Cytokine and Chemokine Concentrations in Serum of
Neonates
We measured the 17 types of the cytokine and chemo-
kine concentrations in the serum of all of the subjects.
PEDIATRICS Volume 121, Number 4, April 2008 e749
The data for each cytokine or chemokine are shown in
Fig 1. Detailed statistical data with regard to cytokine
and chemokine concentrations in sera are given in Table
2. Six types of proinammatory cytokines in the sera of
neonates in the MAS group were signicantly higher
than those in the healthy children: IL-1, IL-6, IFN-,
TNF-, G-CSF, and GM-CSF. The 2 chemokines of IL-8
and MIP-1 were signicantly higher in the MAS group
than in the healthy children. Next, 5 types of proinam-
matory cytokines in the sera of the MAS group were
found to be signicantly higher than in the non-MAS
group: IL-6, IFN-, TNF-, G-CSF, and GM-CSF. The
chemokine IL-8 was also signicantly higher in the sera
of the MAS group than in the non-MAS group. Inter-
estingly, a representative anti-inammatory cytokine,
IL-10, was drastically elevated in the MAS group com-
pared with the non-MAS group. Only 1 cytokine, IL-7,
in both the MAS and non-MAS groups was signicantly
lower than in the healthy children group. No signicant
difference in cytokine and chemokine levels in the sera
was found between the non-MAS and the healthy chil-
dren groups. Moreover, no signicance differences be-
tween cytokine and chemokine concentrations in sera
and the oxygenation index (1.518.7) were found
among the MAS group (data not shown).
DISCUSSION
We found that most types of proinammatory cytokines
(IL-6, IFN-, TNF-, G-CSF, and GM-CSF) and chemo-
kines (IL-8) in sera were signicantly elevated in neo-
nates with MAS compared with neonates without MAS.
In addition, the anti-inammatory cytokine IL-10 was
also signicantly elevated in the MAS group. It has been
suggested that the levels of cytokines and chemokines in
sera might reect the production of cytokines and che-
mokines by inammatory sites such as the lung, liver,
and intestine.
1821
Our results suggest that proinamma-
tory cytokinemia and chemokinemia in MAS may in-
deed reect exacerbation of pulmonary injuries because
of excessive inammation. This may also account for the
simultaneously elevated IL-10 level, possibly to reduce
the excessive inammatory responses in MAS. Thus,
imbalance of these immunologic responders (cytokines
and chemokines) might, in part, be associated with the
pathophysiology of chemical pneumonitis and systemic
inammation in MAS.
2224
The proinammatory cytokines, that is, IL-1, IL-6,
IFN-, TNF-, G-CSF, and GM-CSF, and some chemo-
kines, such as IL-8 and MIP1, are strongly linked to
various inammatory diseases.
23,25,26
These cytokines and
chemokines directly induce complicated inammatory
responses, including cell proliferation, cell differentia-
tion, and cell death. Moreover, these proinammatory
cytokines and chemokines activate cytotoxic T cells (nat-
ural killer cells and lymphokine activated killer cells) and
phagocytes, such as granulocytes and monocytes or
macrophages. These activated leukocytes, in turn, re-
lease toxic proteins (proteolytic enzymes and toxic gran-
ules) and active oxygen species, suggesting that these
cells can induce excessive cellular or tissue damage in
inammatory lesions.
27
For example, tissue injuries seen
in lung disease, such as acute respiratory distress syn-
drome, may be responsible for these abnormal immuno-
logic responses involving aberrant induction of proin-
ammatory cytokines and chemokines and activation or
migration of leukocytes.
28,29
In addition, the exacerba-
tion of rheumatoid arthritis is believed to be because of
the abnormal induction of TNF-, and neutralizing
monoclonal antibody is frequently used in treatment
and is associated with remission.
30,31
However, in MAS,
the relationships between induction of cytokines and
chemokines and pathophysiology are poorly under-
stood, although levels of a few cytokines in sera of MAS
patients have been investigated.
4
The assessment of var-
ious cytokines and chemokines levels is, therefore, im-
portant to precisely understand the mechanisms of lung
injuries in MAS.
IL-4, IL-10, and IL-13 act as anti-inammatory cyto-
kines and prevent abnormal inammatory reactions in
vivo.
32,33
IL-10 is mainly secreted by lymphocytes and
monocytes or macrophages as an anti-inammatory cyto-
kine and blocks inammatory actions, including inhibition
of IL-6 and TNF- synthesis, and downregulates intercel-
lular adhesion molecule-1 and matrix metalloprotein-
ase.
3336
Garingo et al
37
demonstrated the production of
IL-10 by lung inammatory cells from tracheal uid col-
lection in term neonates with MAS, suggesting that eleva-
tion of IL-10 levels may be induced mainly by lung injury
or disseminated systemic inammation because of meco-
nium aspiration, thereby reducing the devastating inam-
matory responses.
11,38,39
In the present study, the presence
of anti-inammatory cytokine IL-10 in the serum of neo-
nates with MAS was noted to be higher than in those
without MAS, suggesting the possibility that elevated IL-10
levels in MAS play a role in preventing the exacerbation of
pulmonary inammation.
Meconium contains variable amounts of cytokines,
chemokines, and other substances, including IL-1,
IL-6, IL-8, TNF-, heme, phospholipase, bile acids, lipids,
and polysaccharides,
10,40
which are associated with the
pathophysiology of MAS.
4,10,38,40
For example, de Beau-
fort et al
10
showed that the addition of meconium in-
duces the production of IL-8 from A549 epithelial cells,
and Zagariya et al
24
demonstrated that mRNA for TNF-,
IL-6, and IL-8 is expressed in A549 epithelial cells stim-
ulated by meconium. These results suggest that meco-
nium itself is inducible for severe inammatory re-
sponses. Thus, the various substances derived from
TABLE 1 Characteristics of Subjects in This Study
Characteristic Nonmeconium
Aspiration
(n 16)
a
Meconium
Aspiration
(n 11)
a
Gestational age, mean SE, wk 39.4 0.3 40.3 0.3
Birth weight, mean SE, g 2740 108 3002 126
1-min Apgar score, median
(interquartile range)
8 (89) 7 (58)
b
5-min Apgar score, median
(interquartile range)
9 (910) 8 (79)
b
a
Nonmeconium aspiration is dened as nonmeconium-stained amnio-uid.
b
P value is .05.
e750 OKAZAKI et al
meconium and host may synergistically affect lung in-
ammation in MAS.
Next, it may be important to address the origins of the
high levels of cytokines and chemokines in serum with
MAS, and some major origins have been suggested.
10,38
Lindenskov et al
12
showed that meconium leakage into
circulating blood because of lung rupture may induce
abnormal production of various cytokines and chemo-
kines from blood cells through activation of comple-
ments, leading to cytokinemia or chemokinemia in
MAS.
38
Moreover, meconium exposure to lung cells,
such as alveolar cells, epithelial cells, and immunologic
cells, may induce overproduction of cytokines and che-
mokines from these cells.
10,40,41
These cytokines and che-
mokines may mainly reect their levels in not only
bronchoalveolar lavage uid (BALF) but also serum.
12,42
Thus, it is possible that overproduction of cytokines and
chemokines in the lung may reect the cytokine and
chemokine levels in serum with MAS, although we did
not measure them in BALF with MAS. Together, high
levels of cytokines and chemokines in serum with MAS
may be mainly responsible for blood cell- and lung-
derived cytokines and chemokines. Detailed studies fo-
cusing on the origin of cytokines and chemokines in
serum with MAS may be needed.
We have demonstrated previously that 2 types of
cytokines (IL-6 and IL-8) and the anti-inammatory
cytokine IL-10 in sera were higher in asphyxiated neo-
nates without MAS than neonates with normal vaginal
delivery.
43
In the present study we have further shown
that other cytokines and chemokines, including IFN-,
TNF-, G-CSF, and GM-CSF, were higher in neonates
with MAS than in those without MAS. It is suggested
that meconium aspiration is a major risk factor for se-
0
2
4
6
8
10
12
P < .05
0
500
1000
1500
2000
2500
3000
P < .005
P < .01
I
L
-
1

,

p
g
/
m
L
I
L
-
6
,

p
g
/
m
L
0
20
40
60
80
100
P < .05
P
P < .05
P < .005
0
10
20
30
40
50
P < .01
P < .005
I
F
N
-

,

p
g
/
m
L
T
N
F
-

,

p
g
/
m
L
Healthy
children
(n = 9)
Non-MAS
neonates
(n = 16)
MAS
neonates
(n = 11)
Healthy
children
(n = 9)
Non-MAS
neonates
(n = 16)
MAS
neonates
(n = 11)
Healthy
children
(n = 9)
Non-MAS
neonates
(n = 16)
MAS
neonates
(n = 11)
Healthy
children
(n = 9)
Non-MAS
neonates
(n = 16)
MAS
neonates
(n = 11)
I
L
-
1
0
,

p
g
/
m
L
0
20
40
60
80
P < .001
P < .01
0
20
40
60
80
G
M
-
C
S
F
,

p
g
/
m
L
P < .001
P < .005
0
500
1000
1500
2000
2500
3000
P < .05
P < .05
G
-
C
S
F
,

p
g
/
m
L
0
5
10
15
P < .001
P < .001
I
L
-
7
,

p
g
/
m
L
Healthy
children
(n = 9)
Non-MAS
neonates
(n = 16)
MAS
neonates
(n = 11)
Healthy
children
(n = 9)
Non-MAS
neonates
(n = 16)
MAS
neonates
(n = 11)
0
1000
2000
3000
4000
5000
I
L
-
8
,

p
g
/
m
L

P < .05
P < .05
0
500
1000
1500
2000
M
I
P
-
1

,

p
g
/
m
L
P < .05
FIGURE 1
Concentrations of various cytokines andchemokines insera of healthy children, neonates without MAS, andneonates withMAS. Detailedsubject data andprocedures for the determinationof cytokine
concentrations inseraaredescribedinTable1andthetext. Vertical bars represent means SEs.
PEDIATRICS Volume 121, Number 4, April 2008 e751
verity of asphyxia.
44
Thus, these additionally elevated
cytokines and chemokines induced by meconium aspi-
ration may reect the severity of MAS in asphyxiated
neonates as a risk factor for exacerbation of pulmonary
injury.
Substances including lactate, protein S-100 (a calcium-
binding protein), and creatine kinase-BB (brain-specic
creatine kinase) are useful markers for evaluating the se-
verity of MAS and asphyxia,
45
although we did not evalu-
ate themin the present study. In addition, there may be an
association between the oxygenation index and cytokine
and chemokine levels in sera.
12
However, no relationships
between this index and any cytokine and chemokine levels
in sera with MAS were found in the present study. This
may be attributed to differences in experimental conditions
including sampling time and samples (BALF or serum).
12,42
To evaluate more precisely the severity of MAS, additional
studies regarding the relationships between cytokines and
chemokines and other markers may be needed.
CONCLUSIONS
In conclusion, we found that most types of proinamma-
tory cytokines and some chemokines were signicantly
elevated in sera in patients with MAS. These inammatory
accelerators may be associated with aggravation of chem-
ical pneumonitis and systemic inammations in MAS, be-
cause elevated IL-10 (an anti-inammatory cytokine) may
reduce them. Thus, the pathophysiology of MAS may be
partially explained by various signicantly elevated proin-
ammatory cytokines, chemokines, and anti-inamma-
tory cytokines in serum. Monoclonal antibodies (eg, hu-
manized monoclonal antibody) against proinammatory
cytokines, chemokines, and complement inhibitors may be
applicable for MAS in the future.
ACKNOWLEDGMENT
We thank Taisei Ishioka for his skillful support.
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4. Vidyasagar D, Lukkarinen H, Kaapa P, Zagariya A. Inamma-
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TABLE 2 Various Cytokine and Chemokine Concentrations in Sera in Neonates With or Without MAS and in Healthy Children (pg/mL)
Cytokines/
Chemokines
MAS, Mean SE,
pg/mL
Non-MAS, Mean SE,
pg/mL
Healthy Children,
Mean SE, pg/mL
P for MAS Versus
Non-MAS
P for MAS Versus
Healthy Children
P for Non-MAS Versus
Healthy Children
IL-1 3.8 1.1 1.7 0.6 0.7 0.4 n.s. .035 n.s.
IL-2 0.1 0.1 n.d. 9.1 6.0 n.s. n.s. n.s.
IL-4 1.3 0.4 0.3 0.1 2.6 1.5 n.s. n.s. n.s.
IL-5 1.1 0.4 1.2 0.2 1.3 0.4 n.s. n.s. n.s.
IL-6 909.5 268.1 213.4 69.4 13.1 7.2 .005 .002 n.s.
IL-7 3.3 0.6 3.1 0.4 10.1 1.4 n.s .001 .001
IL-8 1462.4 536.1 262.2 144.8 7.1 1.6 .019 .013 n.s.
IL-10 31.7 7.8 11.5 2.2 3.1 0.8 .007 .001 n.s.
IL-12 4.3 2.7 2.1 1.0 19.4 11.4 n.s. n.s. n.s.
IL-13 0.3 0.1 0.2 0.1 0.3 0.1 n.s. n.s. n.s.
IL-17 0.9 0.5 0.1 0.1 4.3 4.3 n.s. n.s. n.s.
G-CSF 848.2 331.7 96.0 29.8 2.0 1.2 .011 .012 n.s.
GM-CSF 39.3 7.7 12.9 4.0 n.d. .002 .001 n.s.
IFN- 28.5 9.8 2.8 1.4 5.9 3.7 .005 .039 n.s.
MCP-1 580.6 185.0 369.0 132.7 45.0 6.2 n.s. n.s. n.s.
MIP-1 556.7 159.6 386.0 37.7 160.8 16.6 n.s. .023 n.s.
TNF- 16.5 4.8 3.9 0.8 2.6 1.1 .004 .006 n.s.
Detailed statistical methods are described in the text. MCP indicates monocyte chemoattractant protein; n.s., not signicant; n.d., not detected (lower than limit of sensitivity).
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