LACK OF ASSOCIATION OF TUMOR NECROSIS
FACTOR-α G–308A AND TRANSFORMING GROWTH
FACTOR-β1 C–509T POLYMORPHISMS IN PATIENTS
WITH DEEP NECK SPACE INFECTIONS
Jevtović-Stoimenov T1, Despotović M1,*, Pešić Z2, Ćosić A2
*Corresponding Author: Milena Despotović, M.D., Department of Biochemistry, Faculty of Medicine, University
of Niš, Bulevar dr Zorana Đinđića 81, 18000 Niš, Serbia; Tel.: +381-62-606-036; Fax: +381-18-423-8770;
E-mail: milena.despotovic@ymail.com
page: 59
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INTRODUCTION
Deep neck space infections are defined as infections
that spread along the fascial planes and spaces
of the head and neck [1]. They can arise from various
head and neck regions. The most common etiology
is pharyngitis, tonsillitis, odontogenic infections, upper
respiratory infections, otitis media or trauma.
The deep neck space infections produce significant
morbidity and mortality, particularly when associated
with the predisposing factors that impair a functional
immunological response [2]. Even in the era of antibiotics,
these infections have been potentially lifethreatening
conditions due to the airway obstruction,
jugular vein thrombosis, descending mediastinitis,
sepsis, acute respiratory distress syndrome and disseminated
intravas-cular coagulation [2].Tumor necrosis factor-a (TNF-a) is a multifunctional,
inducible cytosine that is produced in
response to infection, inflammation and injury. Tumor
necrosis factor-a can be produced by lymphoid cells,
mast cells, endothelial cells, fibroblasts and neuronal
tissue [3]. It is mainly produced by the macrophages
in response to activation of membrane-bound patternrecognition
molecules, which detect common bacterial
cell surface products such as polysaccharides,
carbohydrates and lipopolysaccharides (LPS). It is
the main mediator in response to Gram-negative bacteria
and concentration of TNF-a correlates with the
amount of bacteria and the phase of inflammation [4].
Transforming growth factor-b1 (TGF-b1) is a
pleio-tropic cytokine with a variety of effects on a
wide range of cells in the immune system, playing an
important role in cell differentiation, growth, matrix
formation, and regulation of immune and inflammatory
responses [5]. It is also a very potent stimulator
of monocyte, lymphocyte, neutrophil and fibroblast
migration [6].
The genetic control of inflammatory response
in humans has been extensively studied, including
the investigation of TNF-a and TGF-b1 responses.
Numerous studies have shown that the variations in
production and activity of cytokines influence the
susceptibility and/or resistance to a range of infectious
agents, autoimmune diseases, cancer and other
disorders [7]. Differences in the production of cytokines
between individuals are often caused by single
nucleotide polymorphisms (SNPs) in the promoter
or coding regions of cytokine genes that directly affect
the transcription and synthesis of mRNA [8]. A
biallelic polymorphism at the position –308 within
the promoter region of the TNF-a gene is one of the
most investigated. The presence of the polymorphic
TNF-a –308A allele is considered to be associated
with the higher TNF gene transcription and TNF-a
overproduction [9]. This substitution leads to 2- to
3-fold higher transcriptional activity of the TNF-a
upon stimulation with bacterial LPS [10].
The TGF-b1 gene also has several polymorphisms,
including C-988A, G-800A and C-509T. The
cytosine (C) to thymine (T) base exchange at position
–509 relative to the first major transcription start site
of the TGF-b1 gene was found to be differentially
related to transcription factor binding to the TGF-b1
promoter, transcriptional activity of TGF-b1, and
TGF-b1 plasma concentration [11].
Genetic variations within the cytokine genes may
be critical in understanding individual predisposition
and susceptibility to different clinical conditions. To
the best of our knowledge, there are no available
studies examining the distribution of TNF-a G-308A
and TGF-b1 C-509T polymorphisms in patients suffering
from deep neck space infections. Thus, the
aim of this study was to analyze the distribution of
these polymorphisms and their correlation with the
values of inflammatory markers [C-reactive protein
(CRP) and white blood cell (WBC) count] in patients
suffering from infections of deep neck spaces.
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