Page 17 - Portuguese Journal - SPORL - Vol 61. Nº2

response, but this is seen as a phenomenon promotes the production of cytokines such
secondary to chronic inflammation .
13
In type 1 immune response, the cytokines
interferon (IFN)-gamma and interleukin (IL)- inflammation in CRS with polyposis . CRS with
12 are produced in response to viral antigens;
in type 3 immune response, the cytokines are
IL-17A and IL-22 (which target extracellular
bacteria and fungi).
The cytokines produced in the type 2 immune
response are IL-4, IL-5, and IL-13. They are
important in immunity against parasites
and regulate tissue regeneration after injury;
they promote an IgE-mediated inflammatory
response. The type 2 immune response,
formerly called T helper type 2 inflammation,
is driven by inflammatory mediators produced
by Th2 lymphocytes, such as cytokines IL-4,
IL-5, IL-9, and IL-13. In this immune response,
eosinophils play the main role at the cellular
level. An elevation of local IgE level is also
evident, both in the tissues and serum. With
the later identification of other non-Th2 cells
capable of producing the same cytokine
profile (such as type 2 innate lymphoid cells),
the inflammation came to be referred to as
type 2 immune response. IL-5 is an important
cytokine in the differentiation and maturation
of eosinophils at the medullary level. In
addition, it is an activator of eosinophils and
increases their survival in tissues, thereby
reducing the degree of apoptosis. IL-4 leads to
the differentiation of T lymphocytes into Th2,
induces IgE production by B lymphocytes,
plays a role in chemotaxis of eosinophils, and
leads to the recruitment and activation of
mast cells and basophils. IL-13 is chemotactic
for eosinophils, induces B lymphocytes to
produce IgE, and activates mast cells and
basophils. In addition, it promotes mucus
secretion, goblet cell hyperplasia, and collagen
production. IL-33 is also a mediator of type 2
inflammation. It binds to the surface receptors
on Th2 lymphocytes, innate lymphoid cells,
basophils, eosinophils, mast cells, and dendritic
cells, thus activating inflammation in the
airways. Direct exposure to Staphylococcus
aureus at the airway mucosal level appears
to increase the expression of IL-33, which
as IL-5 and IL-13, which in turn play a key role
in the initiation and/or maintenance of type 2
14
type 2 immune response is most commonly
associated with asthma and resistance to
treatment with topical corticosteroids. It
may also be associated with respiratory
disease exacerbated by nonsteroidal anti-
inflammatory drugs. Tissue inflammation is
often associated with remodeling patterns
(fibrosis), polyposis, and fibrin deposition. In
addition to asthma, the other comorbidities
commonly present in patients with CRS with
polyposis are atopic eczema, hives, nodular
prurigo, and eosinophilic esophagitis. It
is generally agreed that in CRS, mucosal
invasion activates the type 1, 2, and 3 immune
responses; however, in CRS this response is
polyclonal rather than a specific and targeted
monoclonal (physiological) response 11,12 .
Treatment
In cases of bilateral chronic diffuse
rhinosinusitis, regardless of having the type 2
endotype or not, the basic treatment includes
topical corticosteroids and nasal lavage
with saline . In addition to pharmacological
1
treatment, exposure to factors that cause
worsening of the disease, such as tobacco and
pollution, should be avoided. International
recommendations differ widely regarding the
use of antibiotics and oral corticosteroids as
the initial pharmacological treatment. In cases
in which initial pharmacological treatment
is insufficient, further investigation with
computed tomography (CT) of the paranasal
sinuses and endotype evaluation ("type 2" or
"non type 2") is indicated. Patients with type 2
endotype (tissue eosinophilia ≥ 10 eosinophils/
high-power field or peripheral eosinophilia ≥
250 or total IgE ≥ 100) tend to be more resistant
to pharmacological therapy and have a higher
post-surgical recurrence rate . 1
There is considerable controversy regarding
the most appropriate time for surgery in CRS. In
a recent study in adults with uncomplicated
15
CRS, it was concluded that endoscopic sinus
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