LACK OF ASSOCIATION OF TUMOR NECROSIS FACTOR-α G308A AND TRANSFORMING GROWTH FACTOR-β1 C509T 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

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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