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EVALUATION OF THE EFFECTIVENESS OF
IMMUNOPROPHYLAXIS IN DISSEMINATED PERITONITIS
O.U. Rakhimo 1, Sh.T. Ti kashe 2, J.R. Kamoljono 3, S.Sh. Mi zaye 4
Tashken S a e Medical Uni e si y1,2,3,4
h ps://doi.o g/10.5281/zenodo.17538689
Abs ac . Gene alized pe i oni is is accompanied by se e e immune sys em dys unc ion,
which inc eases he isk o pos ope a i e complica ions and mo ali y. This s udy assessed he
clinical and immunological e icacy o pe sonalized immunop ophylaxis in 60 pa ien s wi h
a ying deg ees o isk o complica ions, assessed using he IPORP scale. Use o he IPORP
algo i hm allows o di e en ia ion o immunoco ec ion app oaches depending on he se e i y o
he immunopa hology, p o iding a pa hogene ically subs an ia ed, pe sonalized s a egy o he
p e en ion o complica ed pe i oni is.
Keywo ds: gene alized pe i oni is, immunop ophylaxis, IPORP, CD4⁺ T-helpe s, NK cells,
IgM, immunoco ec ion, cy okines, ci cula ing immune complexes.
In oduc ion. I has been scien i ically es ablished ha ea men o gene alized pe i oni is
(GP) includes op imal su gical managemen and comp ehensi e in ensi e ca e. Despi e he s udy
o pa hogenesis, he sys emic in lamma o y esponse, and mode n me hods o o gan deb idemen
and suppo , issues o ea ly ou come p edic ion and iden i ica ion o pa ien s a high isk o
complica ions emain un esol ed. This jus i ies he need o u he clinical and immunological
esea ch and he de elopmen o new p ognos ic algo i hms [1,8]. T ea men o dissemina ed
pe i oni is includes op imal su gical ac ics and comp ehensi e in ensi e ca e. Key pa hogenesis
ac o s, me hods o abdominal deb idemen , an ibac e ial he apy, and o gan suppo ha e been
s udied. Ne e heless, a es o complica ions and mo ali y emain high, indica ing un esol ed
clinical issues [2,5].
The use o immunomodula o y agen s in pe i oni is is limi ed due o he lack o uni o m
app oaches o indica ions and e icacy assessmen . This emphasizes he need o u he clinical
and immunological esea ch and he inclusion o immunological pa ame e s in he s anda d ca e
o such pa ien s [3,6]. The high complica ion a e o dissemina ed pe i oni is and impai ed immune
homeos asis highligh he need o de elop a p ognos ic model based on immunological ma ke s.
Ea ly de ec ion o immunopa hological changes and indi idualized immunop ophylaxis can
educe he isk o complica ions, imp o e ea men ou comes, and inc ease pa ien su i al [4,7].
Aim o he esea ch: Fo e alua ing he clinical and immunological e icacy o
pe sonalized immunop ophylaxis in pa ien s wi h dissemina ed pe i oni is, depending on he
se e i y o immunopa hological changes and he p ognos ic isk o complica ed pos ope a i e
cou se, wi h he aim o s abilizing he in lamma o y p ocess and educing he incidence o
complica ions.
Ma e ials and Me hods: The s udy included 60 pa ien s wi h dissemina ed pe i oni is,
ca ego ized by isk o complica ed cou se using he IPORP scale: low (<10 poin s), high (10–19
poin s), and c i ical (≥20 poin s). The mean age o pa ien s was 52.4 ± 14.7 yea s ( ange: 22–78
yea s), he male- o- emale a io was 32/28. The con ol g oup consis ed o condi ionally heal hy
dono s (n=20) o compa ison o immunological pa ame e s.
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Immune s a us assessmen included a s udy o he cellula and humo al immune sys ems:
- Cellula immuni y: CD3⁺, CD4⁺, CD8⁺ T lymphocy es, NK cells (CD16⁺CD56⁺),
de e mina ion o absolu e coun and pe cen age;
- Humo al immuni y: IgA, IgM, IgG;
- Cy okine p o ile: IL-6, IL-10;
- Ci cula ing immune complexes (CIC).
Immunological pa ame e s we e assessed be o e he apy and on days 3 and 7
pos ope a i ely. Pa ien s in he s udy g oup ecei ed indi idualized immunop ophylaxis
depending on hei isk le el:
Low isk (<10 IPORP poin s): "wai and see" managemen —obse a ion, main enance o
na u al immune balance, nu i ional and elec oly e adjus men s, and limi a ion o sys emic
an ibio ic he apy. High isk (10–19 poin s): basic immunop ophylaxis, including hymic
immunomodula o s (Thymalin 10 mg in amuscula ly once daily o 5–7 days o T-ac i in 1
mcg/kg subcu aneously o 5 days), in a enous IgM-en iched immunoglobulin (Pen aglobin 5
ml/kg/day o 2–3 days), an ioxidan s ( i amins A, E, C).
C i ical isk (≥20 poin s): ex ended immunoco ec ion complex — poly alen IgM/IgA
(Pen aglobin, IgM Oc aga 5 ml/kg/day o 3–5 days), hymic s imulan s, an i-cy okine agen s o
se e e cy okine imbalance, le amisole, and immunomodula o y hepa in. The e ec i eness o he
in e en ion was assessed by changes in CD4⁺, NK, IL-6, IL-10, IgM, and ci cula ing immune
complexes (CIC), as well as clinical indica o s: es o a ion o homeos asis, educ ion in signs o
in oxica ion, and he incidence o pos ope a i e complica ions. The s a is ical da a p ocessing was
pe o med using s anda d desc ip i e s a is ics, co ela ion analysis, and compa a i e es s o
dependen and independen samples. Di e ences we e conside ed signi ican a p<0.05.
Resul s and discussion. Pa ien s wi h an IPORP sco e o less han 10 had isola ed, mino
immune abno mali ies wi hin he physiological no m: CD4⁺ T helpe cells >0.60×10⁹/L, NK cells
~0.25×10⁹/L, IgM 0.9-1.1 g/L, IL-6 ≤30 pg/ml, CIC <55 op . Uni s. Clinically, he eac i e phase
o pe i oni is wi h se ous o se o ib inous exuda e p edomina ed, wi hou gene alized
in lamma ion o in oxica ion, wi h apid es o a ion o homeos asis and a low isk o
complica ions.
In e na ional da a show ha immuno opic he apy in he absence o immunosupp ession
and p edic o s o ad e se ou comes can be excessi e and e en ha m ul. The e o e, a "wai -and-
see" app oach was used in low- isk pa ien s: obse a ion and main enance o na u al immune
balance, discon inua ion o immuno opic agen s, adjus men o nu i ion and luid and elec oly e
balance, and limi a ion o sys emic an ibio ic he apy in he absence o in ec ion. The e we e no
dea hs in his g oup, and he complica ion a e was ≤11%.
I is c ucial o acknowledge ha pa ien s wi h IPORP sco es o 10-19 show signs o ini ial
immunosupp ession wi hin he i s 24 hou s a e su ge y: CD4⁺ T-helpe cells 0.41-0.60×10⁹/L,
NK cells down o 0.25×10⁹/L, and IL-6 down o 60 pg/ml. These changes indica e weakened T-
cell coope a ion, impai ed inna e cy o oxic con ol, and ac i a ion o he p oin lamma o y cy okine
cascade.
In he ea ly pos ope a i e pe iod, e ec i e in e en ions can be implemen ed o s abilize
he in lamma o y en i onmen and p e en sys emic dys unc ion. High- isk pa ien s ecei ed
pa hogen- a ge ed immunop ophylaxis aimed a suppo ing T- and B-cell immuni y and limi ing
media o hype eac ion. The egimen consis ed o hymic immunomodula o s ( hymalin 10 mg
in amuscula ly once daily o 5-7 days o T-ac i in 1 mcg/kg subcu aneously o 5 days), which
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p omo e he p oli e a ion o CD4⁺ T-helpe cells and es o e coope a ion wi h B-cells. The use o
hese d ugs educed he incidence o in ec ious complica ions by mo e han 30%.
The humo al suppo was main ained wi h in a enous IgM-en iched immunoglobulin
(Pen aglobin) a a dose o 5 ml/kg/day o 2-3 days. IgM supplemen a ion imp o es opsoniza ion,
educes ci cula ing immune complexes, and s abilizes he complemen -dependen immune
esponse. An ioxidan suppo was p o ided wi h i amins A (100,000 IU in amuscula ly), E (300
mg o ally), and C (500-1000 mg in a enously). I is gene ally ecognized ha e icacy was
assessed on days 3 and 7 based on CD4⁺, NK, IL-6, IgM, and ci cula ing immune complexes. I
immunosupp ession p og essed, expanded immuno he apy was p esc ibed.
Pa ien s wi h an IPORP sco e ≥20 had signi ican immunopa hological changes: CD4⁺
≤0.40×10⁹/L, NK ≤0.17×10⁹/L, IgM ≤0.60 g/L, IL-6 >90 pg/ml, IL-10 >20 pg/ml, CIC >75 op ical
uni s, which co esponded o he e minal phase o pe i oni is and a high incidence o mul iple
o gan dys unc ion. This condi ion is in e p e ed as pos -agg essi e immunosupp ession wi h
deple ion o inna e and adap i e immuni y. I is impo an o cla i y ha o c i ically ill pa ien s,
an expanded egimen was used: poly alen IgM/IgA (Pen aglobin, IgM Oc aga ) 5 ml/kg/day IV
o 3-5 days; in cases o se e e cy okine imbalance, an i-cy okine agen s as indica ed, hymic
s imulan s, le amisole, and immunomodula o y hepa in. Daily moni o ing o IL-6, IL-10, CD4⁺,
NK, ci cula ing immune complexes (CICs), and IgM allowed o ailo ed in e en ion.
The IPORP-based algo i hm allowed o he iden i ica ion o h ee isk le els: low (<10),
high (10–19), and c i ical (≥20 poin s), and indi idualized immuno he apy. Low- isk pa ien s
ecei ed an immune abs inence s a egy; high- isk pa ien s ecei ed basic immunop ophylaxis
wi h hymic pep ides, IgM immunoglobulins, and an ioxidan s; and c i ical pa ien s ecei ed an
expanded egimen wi h in ensi e immuno he apy. The algo i hm's undamen al dis inc ion is i s
pa hogene ic ocus: compensa ing o immune de iciencies, blocking hype cy okinemia, and
p e en ing he p og ession o he in lamma o y cascade o mul iple o gan ailu e and sep ic
complica ions. IPORP has enabled he ans o ma ion o immunop ophylaxis in o a manageable,
pe sonalized sys em ha e lec s he se e i y o immunopa hology and i s e e sibili y (Table 1).
Table 1
Compa ison o immune esponse indica o s and immunop ophylaxis s a egies depending on
he isk o complica ions
Risk le el
(IPORP)
Numbe
o
poin s
Immunological
indica o s
Clinical pic u e
Immunop ophylaxis
ac ics
Low
<10
CD4⁺ >0.60×10⁹/l,
NK ~0.25×10⁹/l,
IgM 0.9–1.1 g/l, IL-
6 ≤30 pg/ml, CEC
<55
Reac i e phase,
se ous/se o ib inous
exuda e, wi hou
gene aliza ion
Expec an managemen ,
main aining immune
balance, adjus ing
nu i ion and wa e -
elec oly e balance,
limi ing an ibio ics
High
10–19
CD4⁺ 0.41–
0.60×10⁹/L, NK ↓
up o 0.25×10⁹/L,
IL-6 up o 60 pg/ml
Ini ial
immunosupp ession,
p oin lamma o y
cascade
Thymalin/T-ac i in,
IgM immunoglobulin,
an ioxidan s
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C i ical
≥20
CD4⁺ ≤0.40×10⁹/l,
NK ≤0.17×10⁹/l,
IgM ≤0.60 g/l, IL-6
>90 pg/ml, IL-10
>20 pg/ml, CEC
>75
Te minal phase,
high incidence o
mul iple o gan
dys unc ion
Ex ended egimen:
IgM/IgA, an i-cy okine
agen s, hymic
s imulan s, le amisole,
hepa in
The e idence clea ly shows ha be o e inclusion in he immunop ophylaxis egimen, mos
pa ien s in he s udy g oup demons a ed signi ican supp ession o cellula immuni y, compa able
o he con ol g oup. All pa ien s we e classi ied as high o c i ical isk on he IPORP scale,
clinically co esponding o oxic o e minal pe i oni is and accompanied by se e e immunological
diso de s. The mos signi ican di e ence was he CD4⁺ T-helpe cell le el: an a e age o
0.34×10⁹/L wi h a no mal alue o 1.01×10⁹/L, wi h 12 pa ien s ha ing le els ≤0.30×10⁹/L (Table
2).
Table 2
Cellula immuni y s a us in s udy g oup pa ien s be o e and a e immunoco ec ion
compa ed o no mal alues
INDICATOR
REFERENCE
(n=20)
IMMUNOPROPHYLAXIS
Be o e (n=60)
A e (n=60)
Lymphocy es, %
28,2±3,6
17,1±3,9*
25,6±4,1*#
Lymphocy es, ×10⁹/л
2,16±0,52
0,91±0,28*
1,84±0,34*#
CD3+, %
68,4±4,3
49,2±5,7*
64,7±4,6*#
CD3+, ×10⁹/l
1,65±0,37
0,66±0,22*
1,43±0,29*#
CD4+, %
40,1±4,9
26,1±4,3*
37,8±4,4*#
CD4+, ×10⁹/l
1,01±0,28
0,34±0,11*
0,87±0,18*#
CD8+, %
25,3±3,2
20,4±3,4*
24,1±3,3#
CD8+, ×10⁹/l
0,66±0,14
0,29±0,09*
0,52±0,12*#
CD4+/CD8+
1,65±0,21
1,19±0,15*
1,52±0,17#
CD16+/CD56+, %
14,8±2,5
9,2±2,0*
13,7±2,1#
CD16+/CD56+, ×10⁹/l
0,31±0,06
0,16±0,05*
0,27±0,06#
No e: * - p<0.05 s a is ically signi ican alue ela i e o e e ence alues; # - p<0.05
s a is ically signi ican alue ela i e o pa ien s be o e immunop ophylaxis.
In one such si ua ion, a 63-yea -old man who unde wen su ge y o panc ea ic nec osis
con inued o expe ience se e e in oxica ion on he second pos ope a i e day, despi e no malizing
empe a u e eadings. An immunog am e ealed CD4⁺ 0.26×10⁹/L, CD3⁺ 0.58×10⁹/L, and
CD16⁺CD56⁺ 0.12×10⁹/L. The pa ien was ans e ed o an ex ended immuno he apy egimen.
I is widely suppo ed by da a ha be o e he s a o immunop ophylaxis, he pa ien s had
signi ican lymphocy e supp ession. The a e age lymphocy e coun in he whi e blood cell coun
was only 17.1%, almos 1.7 imes lowe han ha o heal hy con ols (28.2%). In absolu e e ms,
he dec ease was e en mo e signi ican : he lymphocy e concen a ion was 0.91×10⁹/L e sus he
e e ence alue o 2.16×10⁹/L, o 2.4 imes lowe han no mal. The CD3⁺ T-lymphocy e coun (a
key popula ion o adap i e immuni y) dec eased by 2.5 imes, om 1.65 o 0.66×10⁹/L, indica ing
sys emic supp ession o T-cell ac i i y.
Al hough he le el o CD8⁺ T-supp esso s also dec eased by almos 2.3 imes, he
magni ude o his dec ease was less signi ican han ha o coope a i e CD4⁺ T-helpe cells. This
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led o an imbalance be ween egula o y and e ec o componen s, as di ec ly indica ed by he
change in he CD4⁺/CD8⁺ a io: i dec eased by 28%. This dynamic e lec s no simply a
quan i a i e de ici , bu a quali a i e ailu e o immune esponse egula ion, cha ac e is ic o he
ini ial immunosupp ession phase in se e e su gical si e in ec ions.
I is b oadly accep ed ha pa icula a en ion should be paid o he inna e immune sys em,
especially na u al kille cells, cha ac e ized by CD16⁺CD56⁺. Be o e immunop ophylaxis, hei
alues we e mo e han hal he e e ence alue, indica ing a p onounced de iciency in he cy o oxic
componen . In mo e han hal o he pa ien s, he le el o hese cells emained c i ically low (less
han 0.20 × 10⁹/L). Fo example, a 72-yea -old man wi h su gical ea men o ecal pe i oni is
seconda y o a colon umo had a CD16⁺CD56⁺ cell popula ion o 0.11 × 10⁹/L, and h ee days
la e , he de eloped a pos ope a i e wound in ec ion and in lamma o y complica ion.
A e comple ing a pe sonalized cou se o immunop ophylaxis, accele a ed cellula
egene a ion was consis en ly obse ed. The absolu e lymphocy e coun inc eased almos wo old,
and he CD3⁺ T-lymphocy e coun ma ched he con ol le el. No ably, CD4⁺ T-helpe cells, which
play a key ole in adap i e immuni y, inc eased mo e han 2.5- old, and he CD4⁺/CD8⁺ a io
e u ned o nea -no mal le els, indica ing a signi ican es o a ion o homeos asis. The unc ion o
CD16⁺CD56⁺ cells is in e es ing: a e ea men , hei coun inc eased by app oxima ely 1.7- old,
and a his le el, a signi ican imp o emen in he pa ien 's clinical condi ion was obse ed in mos
cases (signs o in oxica ion dec eased, hemodynamics s abilized, and body empe a u e e u ned
o no mal). This coincided wi h a dec ease in PCT concen a ions and he sys emic in lamma o y
phase in 75% o pa ien s.
Conclusion. As o he a o emen ioned pa ien wi h panc ea ic nec osis, on day 7 o his
illness, he CD4⁺ coun almos eached he lowe limi o no mal, coinciding wi h he es o a ion
o cy o oxic NK cells and a educ ion in in lamma o y symp oms. The pa ien was sa ely
ans e ed o he eco e y wa d wi hou complica ions. I is commonly unde s ood ha hese
esul s demons a e ha immunop ophylaxis agains pa hogene ically sensi i e componen s o he
immune esponse compensa es no only o quan i a i e de ici s bu also o unc ional
coo dina ion wi hin he T-helpe and inna e e ec o cell sys ems, leading o an imp o ed
in lamma o y esponse and a educed isk o complica ions. In he ea ly s ages o immuno he apy,
pa ien s wi h high and c i ical isk o complica ions demons a ed signi ican impai men o
humo al immuni y. The a e age IgM le el was app oxima ely one- hi d o no mal, and in some
pa ien s i dec eased o 0.65–0.70 g/L, especially in pa ien s wi h se e e panc ea ic nec osis and
ecal pe i oni is, which is almos hal he physiological no m.
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