In the present study we showed the gene expression of cytokines involved in the pathophysiology and immune response of GERD, patients with BE showed an increased expression of IL-8, IL-1β, NF-κβ, IL-10 and MMP-3, patients with EE had higher levels of IL-1B, IL-6, IL-8 and IL-10 and patients with NERD showed a differential gene expression of cytokines Th1, particularly TNF-α and IL-1B and decreased gene expression of Th2 cytokines such as IL-10, IL-8 and MMP9.
Even though, this is a descriptive study, the findings are of interest, as far as we know, additional studies about TH cytokines in the esophageal mucosal inflammatory process.
Although several studies have reported serum levels of inflammatory mediators in patients with GERD., this study analyzed gene expression profiling of inflammatory mediators (IL-1β, IL-6, TNF-α, INF-γ, and NF-κβ) associated with damage of esophageal mucosa from patients with 3 different phenotypes of the disease (BE, EE and NERD) and also compared them with those present in a subgroup of patients with a non-erosive variety who were monitored for 24 hours of pH measures to differentiate cases of esophageal exposure to abnormal acid from normality.
The profile of mediators in BE showed an increased expression of IL-1β, IL-8 and IL-10. These results provide understanding of the pathogenesis of Barrett's esophagus and the possible immunoregulatory role of IL-10 associated with the permanent mucosal damage unable to counteract the aggression of other inflammation mediators.
This is in accordance with a previous reported in a mouse model of Barrett’s esophagus that showed an increased expression of IL -10, as compared to those in non-Barrett's esophagus while there were no differences in the levels of pro-inflammatory cytokines such as TNF-α or INF-γ  .
On the other hand, the expression of MMP3 and MMP9 were increased in BE compared to the control group.
The primary function of matrix metalloproteinases (MMP) is in extracellular matrix (ECM) degradation and remodeling. They are secreted by T cells, neutrophils, keratinocytes, monocytes and macrophages.
It has been proposed that MMP-3 6A/5A polymorphism might also been involved in the presentation of patients with BE.
Additionally, MMP-9 could be involved in the pathogenesis of BE and therefore of esophageal adenocarcinoma as well. We found this protease increased although our group of patients with BE did not showed dysplasia.  Further studies are required to determine if metalloproteins play a role in mucosal damage in BE. Our study highlights the participation of MMP-9 and MMP-3 in patients with BE, possibly forming part of their pathological mechanism for this change of epithelium.
In relation to IL-6 measurements, we found an increased expression of this cytokine in patients with BE as compared to controls.
In this context, Isomoto et al  highlighted the role of IL-6 as an inflammatory mediator of Th1 response that plays an important role in the malignant progression of the esophageal epithelium. In this sample in the BE phenotype does not highlight this participation probably related to patients not presenting dysplasia but only the change of epithelium corroborated by histology.
Chronic inflammation in BE may play a critical role in the progression from benign to malignant esophageal disease. The rate of progression from Barrett’s esophagus to esophageal adenocarcinoma is approximately 0.12– 0.4% per patient-year [14-16].
For this reason, we decided to perform gene expression analysis of nuclear factor NF-κβ in patients with BE, we found an increased expression of NF-kB in the phenotype of BE compared to the other phenotypes and the control group.
Fang et al  proposed an inflammatory profile for esophageal barrier dysfunction by activating NF-kB signaling pathways triggered by mucosal damage from gastroesophageal reflux.
One of the actions of NF-kB is in the proliferation of T cells and in the pro-inflammatory response which in turn acts as a command of the immune response. Definition of the signaling pathways from the release of NF-kB in GERD are still pending.
On the other hand, the erosive phenotype is a classic example of the balance that exists between the expression of Th1 and Th2 response, to the aggression presented (reflux).
In this study we showed an increase expression of pro inflammatory cytokines such as IL-1B, IL-6 and IL-8 in mucosal biopsies of patients with EE.
According to our results, Mönkemüller K, et al; showed that IL-1B and IL-8 expression correlate with the histomorphological changes in esophageal mucosa of patients with Erosive and Non-Erosive Reflux Disease.
Previously, Rieder et al demonstrated the increase production of IL-1B and IL-6 in EE compared to controls and Fitzgerald et al reported an inflammatory profile by increased production of IL-1B, IL-8 and INF-γ in esophageal epithelium and neutrophils of EE patients.
Blanchard et al found an increased plasma cytokine levels of IL-8 in patients with EE and healthy subjects.
Interestingly, we found an increased gene expression of IL-10 in mucosa of patients with EE in compared with controls, these results suggest the possible role of IL-10 as a critical cytokine for immunoregulatory mechanism in the inflammatory chronic response in the esophagus.
Similar to our results, there are reports in Asian populations that show association of IL-1B and IL-10 polymorphisms with an increased risk of erosive reflux esophagitis and gastritis. One of the perspectives of this study is to identify the role of the polymorphisms of IL-1B, IL-8 and IL-10 in Mexican patients with EE and NERD.
Recent studies have provided greater insight into the pathophysiology and symptom generation in NERD.
In patients with NERD, we found a significantly increased expression of IL-1B , TNF-α and MMP-9 in compared with control group.
Conversely, we detected a decreased expression of IL-8, IL-10 and MMP-3 in patients with NERD.
Previously, Kanazawa et al in a Japanese study of patients with NERD with minimal mucosal involvement, as determined by endoscopy , IL-8 mRNA levels were increased compared with NERD patients with no mucosal involvement and with control, but in this study is important to note the subgroup with NERD had not been studied by pH monitoring to truly corroborate this finding in patients who had normal acid exposure.
Interestingly, Kanasawa et al detected an increase expression of IL-8 in NERD compared to asymptomatic subjects without pHmetry studies. Yoshida also found an increase the expression of this chemokine in patients with NERD.
It has also been demonstrated in patients with NERD, that exposure to GER in squamous cells increases the secretion of IL-8 and Il-1B causing an increase in the migration of T cells and neutrophils. Previous work in GERD has shown an increase in the expression of IL-1B, TNF-α, IL-8 and IL-10. [20, 27, 28]
This study showed the gene expression profiling of inflammatory mediators in the esophagus tissue from patients with different phenotypes of GERD.
Is important to consider transcriptomic profiles and their association with clinical outcomes for the possible application of this technology in the development of personalize medicine.