Download Influence of Linex and Enterosgel on humoral immunity in patients

Influence of Linex and Enterosgel on humoral immunity in patients with
chronic pancreatitis
(Влияние препаратов Линекс и Энтеросгель на гуморальный иммунитет у больных
хроническими панкреатитами)
http://www.apteka-parys.com.ua/articles.php?id=11
Beloglazov, V.A. MD, Professor, Head of Department, Nahashova V.E., Gordiyenko A.I., Malitskaya A.P.,
Department of Internal Medicine № 2 of the Crimean State Medical University named after
S.I.Georgievsky, Simferopol
The main specific mechanism of mucosal immune system is production of antigen-specific secretory IgA.
Secretory IgA is characterized by presence of additional secretory component (S) synthesized by
mucosal epithelium and joining to IgA molecule as it passes through the epithelial cells. Secretory IgA is
capable of neutralizing bacterial toxins, viruses, eliminate antigens entering mucosa of the intestinal
lumen as well as stimulate phagocytosis by providing local immunity. The fact that IgA does not activate
the complement system, minimizes the inflammatory component in performance of immune
mechanisms of the mucous membranes.
The key element of immunity system associated with the stomach and intestine (gut-associated
lymphoid tissue, GALT), is that the area of the lymphoid follicle cupula is lined with unique epithelial
entities called follicle-associated epithelium or microfold cells (M-cells). M-cells are responsible for
antigen absorption from the intestinal lumen and its transport into the lymphoid follicle. Antigens
delivered to lymphoid follicles by M-cells are captured by antigen-presenting cells that present them to
T-lymphocytes, resulting in antigen recognition. B-lymphocytes bearing surface IgM begin synthesizing
IgA.
In our previous studies dysfunction of antiendotoxin humoral immunity was revealed in patients with
chronic pancreatitis (CP). At the same timer, concomitant intestinal pathology having potentiating action
on its imbalance in CP patients. It is well-known that endotoxin (ET) of gram-negative intestinal flora is a
powerful factor of chronic inflammation self-maintenance in terms of pathology. Unfortunately, up to
date the problem of reduction of ET impact on the body of such patients has hardly been explored. It
can be assumed that increase in mucosal IgA concentration may enhance intestinal barrier to ET and
thereby reduce their effect on the body.
The objective of our study was to investigate the influence of probiotic Linex (Sandoz) and
enterosorbent Enterosgel ("Kreoma Farm") on the state of systemic and local antiendotoxin immunity in
CP patients.
Materials and Methods
We observed 28 patients with moderate and severe acute CP at the age from 32 to 72 years who were
treated at the gastroenterology department in the hospital of Suvorov district, Kherson. The first group
consisted of 12 patients with CP who received standard treatment. The second group - 16 CP patients
whose treatment included Linex (2 capsules three times a day for 14 days) and Enterosgel (15 g three
times a day for 7 days). 21 people (healthy donors) were examined as a control group.
All patients underwent complete clinical, laboratory and instrumental examination in the exacerbation
period and the case follow-up for 1 month.
CP was diagnosed in accordance with the International Classification of Diseases, X Revision (ICD-10).
We examined patients of chronic pancreatitis of recurrent, unspecified etiology (excluding alcoholic
etiology) - K86.1 code according to ICD-10.
Study material for determination of serum antibodies to endotoxin (anti-ET), classes G, M, A consisted of
the blood from the cubital vein, for determination of secretory Ig, class A - saliva.
Blood and saliva samples were taken three times: 1 - on admission to the hospital; 2 - at hospital
discharge (12-14 days after the 1st test); 3 - 2 weeks after receiving Linex (not earlier than 1 month from
the date of admission).
Antibody to E. coli K30 endotoxin, classes G, M, A, and secretory Ig, class A were determined by ELISA
(CFA) using LPS derived from the biomass of gram-negative bacteria E. coli K30.
Results and discussion
Study results for antiendotoxin humoral immunity in CP patients are shown in the Table.
In both groups, IgG and IgM levels did not significantly differ from the normal level in all study phases
and did not change significantly during the treatment, which matches with the results of our previous
studies.
Serum IgA level significantly increased in all three samples in both groups. Thus, prior to treatment IgA
level in the first clinical group increased by 2.35 times (p <0.01), on day 14 of the treatment - 3.04 times
(p <0.001), after a month of starting treatment - 2.4 times (p <0.01). Similar changes of serum IgA at the
appropriate research stages were reported in the second clinical group. No statistically significant
differences between the groups 1 and 2 of CP patients were registered for this value.
Differences were observed in the value dynamics of secretory IgA. In the group 1, its level in the patients
on admission to the hospital was 1.74 times below norm (p <0.05); after 2 weeks of treatment (at a
discharge) it did not differ significantly from the norm (p> 0.05); and after further 2 weeks (sample 3) it
again decreased to the original level - 1.65 times below normal (p <0.05).
In group 2 of the patients treated with Linex and Enterosgel in addition to standard treatment, secretory
IgA level at the beginning of treatment was significantly lower the norm (1.62 times) (p <0.05). At the
second stage of the study, at discharge, it increased to normal values, and at the third stage it did not
differ significantly from that in the group of healthy donors (p> 0.05).
In our previous works, we have described a significant increase in serum IgA against the background of
normal IgM and IgG levels in patients with remitting acute CP.
On our opinion, high level of anti-ET, IgA class in all clinical groups is a compensatory response aimed at
strengthening the intestinal barrier by forming adequate secretory IgA concentrations.
In this observation of CP patients in both clinical groups, we have determined consistently high titers of
serum IgA. Low levels of secretory IgA in CP patients at admission indicate that in this disease the
protective response in mucous membranes to ET is significantly reduced. This may be due either to
disorder of the terminal phase of differentiation of sIgA + B-cells into IgA-secreting plasma cells, or
impaired synthesis highly-glycosilated transport piece of intestinal surface epithelium.
Persistent normalization of secretory IgA in the second clinical group probably indicates positive
influence of probiotic Linex and enterosorbent Enterosgel on the synthesis of specific secretory IgA as
well as on interaction normalization of intestinal epithelial cells, and antigen-specific plasma cells of the
proper mucous plate.
Thus, application of probiotics and enterosorbents in treatment of acute CP can positively affect the
local humoral immunity and thus reduce the impact of gram-negative intestinal flora ET.
Conclusions
• In moderate and severe CP, high level of serum IgA has been revealed - 2.26 to 3.15 times above the
norm as well as the low level of secretory IgA both during exacerbation of the underlying disease and in
remission - 1.62 to 1.74 times below the norm.
• After comprehensive treatment of CP exacerbation with probiotic (Linex) and enterosorbent
(Enterosgel), persistent increase in SIgA level was observed.