17
Članek prispel / Received
14. 3. 2021
Članek sprejet / Accepted
28. 10. 2022
Abstract
Background: Pro- and anti-inflamma-
tory cytokines play an important role in 
abdominal sepsis. Studies suggest that 
the anti-inflammatory response is more 
detrimental to the patient with abdomi-
nal sepsis than the initial pro-inflamma-
tory response. We therefore studied the 
serum levels of pro-inflammatory and 
anti-inflammatory interleukins in pati-
ents with abdominal sepsis treated by 
abbreviated laparotomy.
Methods: We performed a prospective 
study of 42 patients treated by abbre-
viated laparotomy. The patients were 
divided into a high-risk (more than two 
procedures before abdominal closure) 
group (24 patients) and a low-risk (two 
or fewer procedures) group (18 patients). 
The differences and correlations betwe-
en the serum levels of pro-inflammatory 
Izvleček
Uvod: Pro- in protivnetni citokini igra-
jo pomembno vlogo pri trebušni sepsi. 
Študije kažejo, da je poznejši protivnetni 
odziv za bolnika s trebušno sepso škodlji-
vejši kot začetni pro-vnetni odziv. Zato 
smo preučevali serumske vrednosti pro-
tivnetnih in pro-vnetnih interlevkinov 
pri bolnikih s trebušno sepso, ki smo jih 
zdravili z metodo odprtega trebuha.
Metode: Izvedli smo prospektivno raz-
iskavo 42 bolnikov, zdravljenih z me-
todo odprtega trebuha. Bolniki so bili 
razdeljeni v dve skupini: visoko tvegano 
skupino (več kot dve menjavi sistema 
do dokončnega zapiranja trebuha – 24 
bolnikov) in skupino z nižjim tveganjem 
(dve ali manj menjavi sistema do zapi-
ranja trebuha – 18 bolnikov). Izmerili 
in izračunali smo vrednosti in razmerja 
med pro- in protivnetnimi citokini prvi 
dan in deseti dan po prvem posegu.
Ključne besede: 
intraabdominalna sepsa, operacija, 
metoda odprtega trebuha, 
interlevkin-6, interlevkin-10
Key words: 
intraabdominal sepsis, surgery, 
negative wound pressure therapy, 
interleukin-6, interleukin-10
Naslov za dopisovanje /  
Correspondence
izr. prof. dr. Bojan Krebs, dr.med.
Univerzitetni klinični center Maribor, 
Klinični oddelek za abdominalno in 
splošno kirurgijo
Ljubljanska 5, 2000 Maribor
E-naslov: bojan.krebs@guest.arnes.si
Klinična študija / Clinical study
ACTA MEDICO-BIOTECHNICA
2022; 15 (2): 17–25
https://doi.org/10.18690/actabiomed.238, CC BY 4.0
© 2022 Avtor(ji) / The Author(s)
Citokinski odgovor pri bolnikih, zdravljenih z metodo 
odprtega trebuha zaradi hude sepse, povzročene z 
dogajanjem v trebušni votlini
Interleukin response in patients treated with 
abbreviated laparotomy for severe intraabdominal 
sepsis
Avtor / Author Tomaž Jagrič1, Maksimiljan Gorenjak2, Evgenija Homšak2, Bojan 
Krebs1,3
Ustanova / Institute 1Univerzitetni klinični center Maribor, Klinični oddelek za abdominalno in splošno kirurgijo; 
2Univerzitetni klinični center Maribor, Oddelek za laboratorijsko diagnostiko; 3Univerza v 
Mariboru, Medicinska fakulteta, Katedra za kirurgijo, Maribor, Slovenija;
1University Medical Centre Maribor, The Department of Abdominal and General Surgery; 
2University Medical Centre Maribor, Department of Laboratory diagnostics; 3 University of 
Maribor, Faculty of Medicine, Department of surgery, Maribor, Slovenia;
18
Klinična študija / Clinical study
ACTA MEDICO-BIOTECHNICA
2022; 15 (2): 17–25
INTRODUCTION
Both morbidity and mortality in patients who have 
undergone surgery for severe abdominal sepsis 
and who were treated with abbreviated laparotomy 
(AL) and temporary abdominal closure (TAC) are 
alarmingly high.1-5 Even the expeditious treatment of 
the cause of abdominal sepsis sometimes cannot save 
patients from their demise. In our previous study, we 
showed that the mortality rates in patients after ten 
to 15 days of protracted treatment following AL and 
TAC rise exponentially despite adequate treatment.6 
We postulated that after ten days these patients 
enter a state that has been described appropriately as 
immunological exhaustion and can develop tertiary 
peritonitis or multiple organ failure.6 Our hypothesis 
was that the severe pro-inflammatory reaction activated 
a disproportionally high anti-inflammatory response 
that is activated between 10 and 15 days after surgery. 
This mechanism, which aims to quench the initial 
surge of pro-inflammatory cytokines, is actually more 
detrimental to the patient than the initial inflammation. 
Measurement of serum levels of interleukin 6 (IL-6) and 
interleukin 10 (IL-10) could therefore predict the course 
and prognosis of severe abdominal sepsis in patients 
treated with AL and TAC. To identify the patients 
at risk of a protracted course of abdominal sepsis and 
consequently likely to experience higher mortality, 
we studied the serum levels of pro-inflammatory IL-6 
and anti-inflammatory IL-10 in patients after these 
procedures.
PATIENTS AND METHODS
Patients
This prospective study included 42 patients with severe 
intraabdominal sepsis admitted to the department for 
Abdominal and General Surgery at our University 
Clinical Centre. The enrolment occurred in the 
operating room after the decision was made to perform 
AL with TAC and planned laparotomy. It was 
followed by the principle of intraabdominal sepsis 
treatment consisting of two steps: i) source control 
and ii) damage control. In the source control step, 
Rezultati: Smrtnost je bila bistveno višja v skupini z visokim 
tveganjem (41,7-% v skupini z visokim tveganjem v primer-
javi s 5,6-% v skupini z nizkim tveganjem; p = 0,012). V 
skupini z visokim tveganjem (22,5 pg/ml (IQR 5,25)) so bile 
ravni IL-10 v serumu bistveno višje kot v skupini z nizkim 
tveganjem (12,15 pg/ml (IQR 6,725)) (p = 0,012). Starost 
je bila pomembno povezana s smrtnostjo (p = 0,007). Loga-
ritmična vrednost ravni IL-10 v serumu prvi dan (HR: 2,5; 
95 % IZ: 1,109–5,638; p = 0,027) in mejna vrednost IL-10 
(HR: 3,816; 95 % IZ: 1,047–13,910; p = 0,042) sta bili v 
multivariatni analizi pomembno povezani s slabšim potekom 
bolezni.
Zaklju~ek: Bolniki, ki imajo prvi dan po posegu večji pro-
tivnetni odziv, imajo tudi dolgotrajnejši potek in višjo stopnjo 
umrljivosti. Koncentracija IL-10 v serumu prvi dan po oper-
aciji lahko napove slabši potek bolezni pri teh bolnikih in bi 
lahko bila uporaben pripomoček pri načrtovanju zdravljenja.
and anti-inflammatory cytokines on days one and ten after the 
initial procedure were assessed.
Results: The mortality was significantly higher in the high-
-risk group (41.7% vs. 5.6% in the low-risk group; p = 0.012). 
IL-10 serum levels were significantly higher in the high-risk 
group (22.5 pg/mL (IQR 5.25)) compared to the low-risk 
group (12.15 pg/mL (IQR 6.725)) (p = 0.012). Age was 
significantly correlated with mortality (p = 0.007). The logari-
thmic value of IL-10 serum levels on day one (HR: 2.5; 95% 
CI: 1.109–5.638; p = 0.027) and the IL-10 cut-off value 
(HR: 3.816; 95% CI: 1.047–13.910; p = 0.042) were signi-
ficantly correlated with worse disease course in multivariate 
analysis. 
Conclusion: Patients who exhibit a greater anti-inflammatory 
response on day one are at increased risk of a protracted course 
and higher mortality. IL-10 serum levels on day one after surgery 
predict a worse disease course in these patients and could be a 
useful marker of abdominal sepsis.
19
the cause of intraabdominal sepsis was treated with 
an appropriate surgical approach (resection of the 
damaged viscus, suturing, faecal diversion, removal of 
necrotic tissue). In the damage control step, a thorough 
washing of the abdominal cavity with sterile normal 
saline was undertaken, necrotic tissue removed as 
a step in reducing the infective burden, and finally, 
the laparotomy was left open and a negative pressure 
device applied. TAC was achieved with a negative 
wound pressure device that was applied in all patients 
using the same technique. The abdominal viscus was 
covered with a sterile permeable foil that prevented 
ingrowth into the polyurethane sponge and fistula 
formation (visceral protective layer). The second layer 
consisted of a permeable sterile polyurethane sponge 
that was placed below the abdominal wall. This sponge 
was in close contact with the third layer of permeable 
polyurethane sponge that was placed at the level of 
the laparotomy. This third layer was sealed off with 
an adhesive abdominal drape onto which an interface 
pad was applied. This was connected with tubing set to 
a negative wound pressure device (RENASYS, Smith 
and Nephew, London UK). The dressing was regularly 
changed at 48-hour intervals until the abdominal cavity 
was free from infective material and the source of the 
sepsis definitely treated. The negative pressure was held 
between 90 and 125 mmHg between dressing changes.
For further analysis, patients were allocated to one of 
two groups. The first group consisted of patients who 
only required one or two additional negative wound 
pressure device changes before definitive laparotomy 
closure. This group was defined as the low-risk group (18 
patients). Patients who required three or more negative 
wound device changes or who died at any time during 
the treatment regardless of the number of dressing 
changes were included in the second group. This group 
was defined as the high-risk group (24 patients). 
The primary endpoint of the study was analysis of the 
difference between serum levels of pro-inflammatory 
IL-6 and anti-inflammatory IL-10 on days one and ten 
between high-risk and low-risk groups. The secondary 
endpoints were the correlations between IL-6 and 
IL-10 serum levels and different clinical parameters, 
and mortality rates in patients with different IL-6 
and IL-10 levels. All patients' data was prospectively 
collected and stored in the hospital database. Informed 
consent was waived because of practical problems. 
Most of the patients were operated on in emergency 
situations and it was impossible to ask incapacitated 
patients for informed consent. However, the study was 
approved by the Institutional Review Board (UKC-MB-
KME-18-05/16).
Serum Interleukin-6 and Interleukin-10 measurement
Serum samples were collected from the patients on the 
first day after the initial operation requiring negative 
pressure therapy and on day ten. Whole blood samples 
were collected into tubes and centrifuged at 2,700 × 
g for 10 min. Serum was then removed and frozen at 
−80 °C until the final analysis. For the determination 
of IL-6 and IL-10 levels, we used a solid-phase, enzyme-
labelled chemiluminescent sequential immunometric 
assay (Immulite 1000 analyzer, Siemens Healthcare 
Diagnostics Inc., Newark, NJ, USA) according to the 
manufacturer's instructions.
Statistical analysis
Based on the results of Inukai et al. and Waio et al.2,18, 
we expected a 40% mortality rate in the high-risk group 
and 4% mortality in the low-risk group. To achieve a 
statistical power of 80% to detect an effect at an − level 
of 5%, at least ten patients were needed in each group. 
We included a total of 42 patients which ensured a 
statistically adequately powered study.
Normally-distributed continuous variables are expressed 
as mean ± SD and variables without a normal distribution 
as median ± IQR. All variables were tested for normality 
distribution with Q-Q Plots. Discrete variables are 
expressed as absolute number and percentage. For 
comparison of normally-distributed continuous 
variables, Student's t-test and one-way ANOVA were 
used; otherwise, the Mann-Whitney U-test was used. 
For comparison of discrete variables, the −x2-test was 
used. Correlations between different parameters were 
analysed with the Pearson's test. Variables that were 
found to be significant and variables with a p value 
below the threshold of 0.4 were included in multivariate 
analysis. Correlations between a continuous outcome 
and multiple predictors were analysed with the linear 
regression model, while correlations between a discrete 
outcome and multiple predictors were analysed using a 
logistic regression model. For the level of significance, 
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Klinična študija / Clinical study
a p value of < 0.05 was selected. Statistical analysis was 
performed using SPSS v. 20 (IBM SPSS Statistics for 
Windows, Armonk, NY, USA). Graphs of interleukin 
serum concentrations were plotted using Excel 2010 
for Windows 10 (Microsoft Corporation, Redmond, 
WA, USA).
RESULTS 
Patients
The baseline characteristics of patients allocated to 
TAC treatment are presented in Table 1. From the 43 
patients originally included, one was excluded from the 
study because he was transferred to another hospital for 
definitive care. Of the remaining 42 patients, IL-6 and 
IL-10 samples were obtained at day one in all cases. If a 
patient died because of sepsis before the second sample 
could be obtained on day ten, only one sample was 
analysed. The second sample on day ten was obtained 
from 34 (80.9%) patients. The mean age of the included 
patients was 62.9 ± 16 years. The main cause leading 
to the requirement for the operation was stercoral 
peritonitis that occurred in 19 (44.2%) patients. In most 
of the patients, the abdominal cavity was contaminated 
without adhesions which corresponded to stage Ib of 
the Bjork classification (18 (41.9%)). The mortality in 
the patient population was 25.5%, and the laparotomy 
was successfully closed on day 7.18 ± 7.24 in survivors. 
Primary closure was achieved in all surviving patients, 
and no surgical complications were observed. With the 
Table 1. Baseline characteristics of patients allocated to TAC treatment.
All patients treated with TAC
Patients treated with TAC
pLow-risk patients 
(less than three 
TAC changes)
High-risk patients
(three or more TAC 
changes)
Age �years±SD � 62±15.9 62.89±14 63.33±17.8 NS
Cause of peritonitis �n (%)�
Purulent
Stercoral
Biliary
Pancreatitis
Intestinal ischemia
12 (27.9)
19 (44.2)
5 (11.6)
3 (7)
4 (9.3)
9 (50)
5 (27.8)
1 (5.6)
2 (11.1)
1(5.6)
3 (12.5)
13 (54.2)
4 (16.7)
1 (4.2)
3(12.5)
NS
Number of TAC changes 
�n±SD� 2.74±2.55 1.28±0.46 3.92±2.9 <0.0001*
Severity of peritonits �n (%)�
Bjork Ia
Bjork Ib
Bjork Ic
Bjork IIb
Bjork IIc
8 (18.6)
18 (41.9)
15 (34.9)
1 (2.3)
1 (2.3)
6 (33.3)
5 (27.8)
7 (38.9)
0 (0)
0 (0)
2 (8.3)
12 (50)
8 (33.3)
1 (4.2)
1 (4.2)
NS
Mortality �n (%)� 11 (25.6) 1 (5.6) 10 (41.7) 0.009*
IL-6 day one �pg/mL (IQR)� 631 (2065) 575 (116.35) 670 (245.9) NS
IL-6 day ten �pg/mL (IQR)� 30.5 (71.45) 25.4 (10.1) 44.65 (16.8) NS
IL-10 day one �pg/mL (IQR)� 16.5 (22.5) 12.15 (6.725) 22.5 (5.25) 0.012*
IL-10 day ten �pg/mL (IQR)� 5.5 (7.32) 5 (5) 6.05 (5.15) NS
NS-nonspecific
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Figure 1.a)IL-6 serum levels on days one and ten of 
patients allocated to TAC treatment.
Klinična študija / Clinical study
exception of one patient who wished to finish treatment 
at another hospital, there were no protocol violations. 
The study ended on January 27, 2019, when the last 
patient was allocated to treatment.
The interleukin levels were the highest on day one after 
the initial operation and then returned to baseline 
levels by day ten after surgery, regardless of the number 
of reoperations. The median serum levels of IL-6 were 
585 pg/mL (IQR 3551.5) on day one and 38.45 pg/
mL (IQR 78.4) on day ten after surgery (Figure 1a). The 
median serum levels of IL-10 were 17.15 pg/mL (IQR 
20.63) on day one and 6.7 pg/mL (IQR 7.6) on day 
ten after surgery (Figure 1b). The ratio of IL-10:IL-6 on 
day one was the highest in patients with pancreatitis 
(13.37 (IQR 28) and lowest in patients with purulent 
peritonitis (0.82 (IQR 3.26); p = 0.008). 
Comparison of clinical parameters and differences in 
IL-6 and IL-10 serum levels between low-risk and high-
risk groups
The distribution and interleukin levels in the low-risk 
and high-risk groups are presented in Table 1. There 
were no statistically-significant differences in age, cause 
of peritonitis or severity of peritonitis according to the 
Bjork classification distribution. The average number 
of TAC changes in the low-risk group was 1.28 ± 0.46, 
while it was 3.92 ± 2.92 in the high-risk group (p < 
0.0001). Mortality was significantly higher in the high-
risk group (41.7% in the high-risk group vs. 5.6% in 
the low-risk group; p = 0.012). Although the patients 
in the high-risk group had higher IL-6 serum values on 
day one than patients in the low-risk group (high-risk 
group: 670.5 pg/mL (IQR 245.9) vs. low-risk group: 
575 pg/mL (IQR 116.35); p = 0.213), this difference 
did not reach statistical significance. The serum values 
of IL-6 on day ten were equal in both groups (Figure 
2a). This implied that the IL-6 levels had returned 
to baseline by day ten after surgery, regardless of the 
severity of the initial disease or the cause of peritonitis. 
Compared to the low-risk group (12.15 pg/mL (IQR 
6.725); p = 0.012), IL-10 serum levels were significantly 
higher in the high-risk group (22.5 pg/mL (IQR 5.25)). 
Similar to IL-6, IL-10 serum values had also returned to 
baseline levels by day ten (Figure 2b).
Figure 1.b) IL-10 serum levels on days one and ten of 
patients allocated to TAC treatment.
Figure 2.a)IL-6 serum levels on days one and ten in 
high-risk and low-risk groups.
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Table 2. Correlations between clinical parameters and serum IL-6 and IL-10 levels of patients allocated to TAC treatment.
IL-6(day 1) IL-6(day 10)
IL-10(day 
1)
IL-10(day 
10) Age
Type of 
peritonitis
Severity of 
peritonitis
Number of 
changes
High-risk 
group Mortality
IL-6(day 1) NS <0.0001* NS 0.044* NS NS NS NS NS
IL-6(day 10) NS NS NS 0.041* NS NS NS NS NS
IL-10(day 1) <0.0001* NS NS NS NS NS NS NS NS
IL-10(day 
10) NS NS NS NS NS NS NS NS NS
Age 0.044* 0.041* NS NS NS NS NS NS NS
Type of 
peritonitis NS NS NS NS NS NS NS NS NS
Severity of 
peritonitis NS NS NS NS NS NS NS NS NS
Number of 
changes NS NS NS NS NS NS NS NS NS
High-risk 
group NS NS NS NS NS NS NS NS 0.008*
Mortality NS NS NS NS NS NS NS NS 0.008*
 NS-nonspecific
Correlations between IL-6 and IL-10, clinical character-
istics, outcome and multivariate analysis
Significant correlations were observed between IL-6 
and IL-10 on day one after surgery (p < 0.0001). The 
serum levels of IL-6 on days one (p = 0.044) and ten 
(p = 0.041) were found to be significantly correlated 
with age. Age was also significantly correlated with 
mortality (p = 0.007). We observed a significant positive 
correlation between mortality and more than three 
dressing changes – “high-risk group” (p = 0.008). The 
type of peritonitis was significantly correlated with the 
ratio between IL-10 on day one and IL-6 on day one 
(p = 0.008) and similarly with the IL-6 day one to IL-6 
day ten ratio (p = 0.016). The ratio of IL-10 to IL-6 
on day one determines the relative proportion of the 
anti-inflammatory response to the pro-inflammatory 
response. Lower ratios signify a proportionally greater 
pro-inflammatory response. The IL-6 day one to IL-6 day 
ten ratio gives a normalised IL-6 value that indicates the 
initial rise of the pro-inflammatory IL-6 as a response to 
sepsis. Table 2 presents correlations between different 
parameters. 
Figure 2.b) IL-10 serum levels on days one and ten in 
high-risk and low-risk groups.
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Figure 3. Scatter plot of the IL-6 serum levels on day 
one and age of patients allocated to TAC treatment.
Receiver operating characteristic (ROC) curve analysis 
was used to determine threshold levels of IL-10 on day 
one for a worse course of sepsis. For the cut-off, a serum 
level of 15 pg/mL was chosen with an area under the 
curve (AUC) of 0.728 (p = 0.012). The sensitivity and 
specificity for prediction of a worse course were 70.8% 
and 61.1% respectively. 
All significant factors were included in the multivariate 
analysis. The linear regression model confirmed a 
significant correlation between IL-6 and age (HR: 0.308; 
95% CI: 0.000–0.001; p = 0.044). Figure 3 shows a 
scatter plot of the IL-6 serum levels on day one and age 
with a regression line. From the included parameters 
in the logistic regression model, the logarithmic value 
of serum IL-10 levels on day one (HR: 2.5; 95% CI: 
1.109–5.638; p = 0.027) and the IL-10 cut-off value 
(HR: 3.816; 95% CI: 1.047–13.910; p = 0.042) were 
significantly correlated with worse sepsis course. 
DISCUSSION
In order to identify patients at risk for a protracted 
course of abdominal sepsis and higher mortality, we 
investigated the postoperative inflammatory response 
and the IL-6 and IL-10 serum levels as markers of 
severity of the inflammatory response. In our previous 
Klinična študija / Clinical study
study, we showed that more than six TAC device 
changes are a significant predictor of mortality in 
patients with severe abdominal sepsis.6 The negative 
impact of prolonged TAC treatment is evident by 
the significantly higher morbidity of patients in the 
present study with more than three TAC changes and 
prolonged treatment. Our results even indicate that 
the number of TAC changes has a stronger impact on 
the disease course than the cause of peritonitis, the 
gravidity of peritonitis and age. This is surprising, since 
some forms of intraabdominal sepsis have been shown 
to have a worse prognosis.3 Comorbidities, age and the 
general condition of the patients have also been proven 
to be significant factors in the prognosis of patients 
with severe sepsis.2 Therefore, other factors must have 
played a more important role in patients’ prognosis 
in our study. As both the high- and low-risk groups in 
our study were matched for age, cause of peritonitis 
and severity of peritonitis, the surgical treatment and 
the immunological response to the surgery must have 
played a more important role in prognosis.
The course of sepsis in surgical patients differs to that 
in patients with non-surgical disease.17 The surgical 
treatment itself causes an immunological response that 
can be detrimental for the patient. Some patients with 
catastrophic intraabdominal sepsis are characterised 
by a protracted course at the end of which, despite 
adequate treatment of the original causative agent, 
tertiary peritonitis and multiple organ failure usually 
ensues. We propose that the trigger for the therapy 
failure is the exaggerated anti-inflammatory response 
activated around  day ten after AL (abdominal lavage) 
and TAC.
Until recently, the accepted model of the host immune 
response to sepsis was biphasic.7 In the first phase 
after infection, the systemic inflammatory response 
targets the causative organisms aiming to remove 
the virulent agents.7 The surviving patients enter an 
immunosuppressive phase in which they can succumb 
to tertiary peritonitis despite adequate treatment of 
the primary cause of sepsis.7 In our patient group, 
we also noticed a rise of pro-inflammatory IL-6 on 
day one after surgery. The IL-6 levels then decreased 
to baseline by day ten. However, high-risk patients in 
our study had only insignificantly higher levels of pro-
inflammatory IL-6 than low-risk patients on day one. 
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While the pro-inflammatory response was greater in the 
high-risk group, this difference did not reach the level 
of significance. This is somewhat counter-intuitive, 
because we would expect a higher inflammatory 
response in patients with a worse course of sepsis. Many 
studies have shown that the increase of IL-6 on the first 
day is prognostic for higher morbidity.9,11,16 In these 
studies, however, heterogeneous groups of patients 
were studied, many of which did not need surgical 
treatment.9,11,16  This shows that a different mechanism 
beside the pro-inflammatory response might have a 
more detrimental effect on the disease course in severe 
abdominal sepsis in patients treated with AL and TAC. 
We also observed that the level of IL-6 response is 
significantly associated with age, which could account 
for a more heterogeneous response in patients with 
abdominal sepsis. Therefore, the serum IL-6 levels on 
day one might be too unreliable to predict a worse 
course in patients treated with AL and TAC. 
In our study group, we found significantly higher 
levels of IL-10 in patients with worse disease course, 
but the levels of IL-10 were increased much sooner 
than expected. We noticed a correlation between 
IL-6 and IL-10 already on day one, implying that the 
inflammatory and anti-inflammatory cascades are 
activated simultaneously in the initial phase of severe 
abdominal sepsis. Similar observations were made by 
Tamayo et al., Cavaillon et al. and Rodriguez-Gaspar 
et al., which also support the model of simultaneous 
activation of pro- and anti-inflammatory responses.12,14 
In our study, the anti-inflammatory cytokine IL-10 
peaked on day one after surgery and was significantly 
higher in patients with worse disease course. These 
levels dropped to baseline by day ten and were similar 
to those of the low-risk group on day ten. This supports 
the observations that the anti-inflammatory response 
occurs simultaneously with the pro-inflammatory 
response, as reported by Tamayo et al., Cavaillon et al. 
and Rodriguez-Gaspar et al.12,14 In addition, we observed 
that this anti-inflammatory response plays a much more 
important role in determining the further course and 
the outcome of severe abdominal sepsis than the pro-
inflammatory response. The logarithmic function of 
serum IL-10 levels was found to be a significant predictor 
for a high-risk course of severe abdominal sepsis in 
multivariate analysis. By ROC analysis, we determined 
the threshold level of serum IL-10 to be 15 pg/mL for 
the high-risk course. This threshold level proved to be 
a significant predictor of a worse course of abdominal 
sepsis in multivariate analysis. The greater impact of the 
anti-inflammatory cytokine IL-10 in patients with sepsis 
was also observed by Li et al.15 They also showed that the 
IL-10 to T-lymphocyte ratio is a significant predictor of 
mortality.15 IL-10 might be a marker of excessive TH2 
cell subset activation. Many recent studies have shown 
that upon engaging with the major histocompatibility 
complex II on the surface of antigen-presenting cells, 
different T cell subsets are activated.19 The largest group 
of T cells in the body is the CD4+ T cell population, 
most of which are the so-called T helper cells (TH). The 
response to antigens varies according to the balance 
of two main TH subsets, TH1/TH2. In some cases, 
there is an overexpression of TH2cells, specifically the 
regulatory TR1 cells. These cells produce IL-10 that 
quells the T-cell response. This is in accordance with 
the results of our study. In future studies, it might be 
valuable to search for the exact mechanism responsible 
for the excessive TH2 activation in severe abdominal 
sepsis.
Another important implication of our findings is that 
due to the early IL-10 response in severe intraabdominal 
sepsis, serum IL-10 levels could serve as a convenient 
marker for worse prognosis in patients treated with AL 
and TAC devices.
From the results presented in our study we can conclude 
that the anti-inflammatory response plays a very 
important role in the course of severe intraabdominal 
sepsis in patients with AL and TAC devices. Patients 
who exhibit a greater anti-inflammatory response on 
day one are at higher risk for a protracted course and 
higher mortality rates, and high IL-10 levels on day one 
could serve as an important marker for worse prognosis.
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2022; 15 (2): 17–25
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Klinična študija / Clinical study
ACTA MEDICO-BIOTECHNICA
2022; 15 (2): 17–25