RAMB - DEZEMBRO

role

regulatory

cells

interleukin

-10

and

vivo

scintigraphy

autoimmune

and

idiopathic

diseases

– T

herapeutic

perspectives

and

prognosis

ssoc

ras

2017; 63(12):1090-1099

1095

As previously mentioned, patients with clinically con-

trolled RA had an increased T

reg

profile; however, the

authors found a differential expression of receptors on

the surface of peripheral blood lymphocytes from indi-

viduals with a diagnosis of MG, with a symptom of mus-

cle weakness, and who were treated with prednisone and

azathioprine, which are immunosuppressive agents. They

showed a decreased profile of T

regs

and CD4

IL-10, as well

as increased CD8

CTLA-4

T cells.

As a consequence of previous studies,

the authors

also reported the role of these two receptors in idiopathic

diseases, such as Bell’s palsy. Patients with autologous

induction of IL-10, obtained through receptor purification,

have been shown to have clinical improvement as well as

increased T

reg

expression. CD4

T lymphocytes were found

to present increased expression after one week of induc-

tion. Paralysis affects the facial nerve (cranial nerve VII),

which results in inability to control the facial muscles on

the affected side. Several other conditions can also cause

facial paralysis, for example, brain tumor, stroke and Lyme

disease. A person may experience pain behind the ear a

few hours before muscle weakness occurs. Clinical treat-

ment includes prescribing anti-inflammatory drugs such

as prednisone. Also, as in MG, immunosuppressive treat-

ment has been used and is effective in controlling symp-

toms and reducing exacerbations. Pyridostigmine is re-

served for refractory cases. The different dosages of

glucocorticoid (daily use, alternating use or pulse thera-

py) do not seem to yield different efficacies.

53-55

The re-

ceptor-glucocorticoid complex enters the cell nucleus and

causes some changes in the DNA that stimulate or repress

the synthesis of certain tissue proteins. Prednisone is

particularly effective as an immunosuppressant and alters

the performance of the immune system, with a decrease

in mediators for inflammation. This decrease, in certain

cases, prevents the communication with other cells of the

immune system that should be recruited in order to

modulate the inflammatory process through the produc-

tion of physiological proteins, such as interleukin 10

(IL-10). Prednisone is used in autoimmune and inflam-

matory diseases and, at a given moment, induces immu-

nological immunosuppression states, precisely because

it prevents the receptors fixed on the surface of the defense

cells and soluble cofactors from playing their roles in

cellular activation, considering that the analogous recep-

tors of the drug can share the same ligands of IL-10, pre-

venting its action. Prednisone is biotransformed in the

liver into prednisolone by the action of the enzyme dehy-

drogenase 11-beta-hydroxysteroid type 1. From 1 to 3

hours after administration, the drug reaches plasma peaks.

Its plasma half-life is approximately 3 hours, its biologi-

cal half-life thus being 12 to 36 hours in this case.

Receptors are surface proteins that bind to external

signaling molecules of high affinity cells and convert this

extracellular event into one or more intracellular signals

that alter the behavior of the target cell. Note that the

receptors for IL-10 are arranged as two-chain

-tetramers

(IL-10 receptor

-chain) and two

-chains (IL-10 receptor

-chain) (Figure 2). Signaling occurs through interaction

with Janus kinases. IL-10 belongs to these two receptor

chains, which associate the

Jak-1

and

Tyk-2

kinases of the

Janus family.

STAT-3

is the main “downstream” signaling

molecule induced by IL-10, which is produced mainly by

regulatory T cells but also by macrophages and keratino-

cytes present in epithelial tissue.

STAT-3

is expected to

act to inhibit gene transcription of inflammatory and/or

autoreactive receptors, forming the

STAT

complex in as-

sociation with

Jak-1

and

Tyk-2

, with consequent nuclear

translocation and gene activation, since mRNA of these

enzymes were detected by RT-PCR, with bands of around

120KDa, with anti-janus-kinase1. The high expression of

CD4

CD25

+low

and CD4

IL-10

+ high

T cells found after in-

duction of autologous IL-10 can be explained by occupy-

ing both R1 and R2 IL-10 receptors. Also, in many cases,

the generation of autoreactive antibodies or T cells can also

be attributed to the role played by infectious agents present

in the body of the individual, such as bacteria, which lead

to the generation of antibodies and T cells which, in turn,

react with many different epitopes of the infectious organ-

ism. If one of these antigens is similar to an autoantigen

it may result in an autoimmune response.

Ex vivo monitoring of IL-10 can be obtained by anal-

ysis of human peripheral blood mononuclear cells, grown

in vitro and induced by blastogenesis for the production

of proteins (interleukins), through mitogenic stimulation

with PHA (phytohemagglutinin). Protocols developed for

in vitro and in vivo experimental phase were filed with

patent application PI0206722-6, supported by experiments

with animal models highly homologous to the human

genome.

The protein fraction of IL-10 obtained by PCR

and purified, free of contaminants can be analyzed by

electrophoresis and quantified by UV-visible spectrometry.

The procedure may become a routine.

Falcão et al.

demonstrated that IL-10 suspensions, ex

vivo, can be applied at the inflammatory site, connective

tissue and muscle. In cases of syndromes that render the

synapses between first-order neurons in the periphery un-

feasible, the application was close to the areas of muscle,

subcutaneous or intradermal flaccidity.

Assuming a regu-

lar interval of 10 days between applications, the monitoring