Circulating blood levels of IL-6, IFN-γ, and IL-10 as potential diagnostic biomarkers in gastric cancer: a controlled study.

BACKGROUND: Gastric adenocarcinoma is the third most common cause of cancer-associated death worldwide. Helicobacter pylori infection activates a signaling cascade that induces production of cytokines and chemokines involved in the chronic inflammatory response that drives carcinogenesis. We evaluated circulating cytokines and chemokines as potential diagnostic biomarkers for gastric cancer. METHODS: We included 201 healthy controls and 162 patients with distal gastric cancer who underwent primary surgical resection between 2009 and 2012 in Mexico City. The clinical and pathological data of patients were recorded by questionnaire, and the cancer subtype was classified as intestinal or diffuse. Pathological staging of cancer was based on the tumor-node-metastasis staging system of the International Union Against Cancer. Concentrations of IL-1ß, IL-6, TNF-α, IL-10, and MCP-1 in serum were measured using multiplex analyte profiling technology and concentrations of IL-8, IFN-γ, and TGF-ß in plasma were measured using enzyme-linked immunosorbent assay. RESULTS: Levels of IL-1ß, IL-6, IFN-γ, and IL-10 were significantly higher and that of MCP-1 was lower in gastric cancer patients compared with controls. No differences in IL-8 or TNF-α levels were observed between gastric cancer and controls. IFN-γ and IL-10 were significantly higher in both intestinal and diffuse gastric cancer, whereas IL-1ß and IL-6 were higher and TGF-ß lower only in intestinal gastric cancer; MCP-1 was lower only in diffuse gastric cancer. IFN-γ and IL-10 levels were significantly higher in early (I/II) and late stage (III/IV) gastric cancer; IL-1ß and IL-8 were higher and MCP-1 was lower only in late stage (IV) patients. Receiver-operating characteristic analysis showed that for diagnosis of GC, IL-6 had high specificity (0.97) and low sensitivity (0.39), IL-10 had moderate specificity (0.82) and low sensitivity (0.48), and IL-1ß and IFN-γ showed low specificity (0.43 and 0.53, respectively) and moderate sensitivity (0.76 and 0.71, respectively). CONCLUSIONS: Increased levels of IL-6, IFN-γ, and IL-10 might be useful as diagnostic biomarkers for GC; however, this needs to be confirmed with larger number of patients and with control groups other than blood donors, properly age paired. IL-1ß, IL-6, MCP-1, and TGF-ß differentiate intestinal from diffuse GC. IFN-γ and IL-10 might be useful for diagnosis of early stage GC, and IL-1ß, IL-8, and MCP-1 for late stages of the disease.

Identification of Mycobacterium tuberculosis in the cerebrospinal fluid of patients with meningitis using nested PCR.

Tuberculous meningitis (TBM) is the most severe form of tuberculosis. It is caused by Mycobacterium tuberculosis (M. tuberculosis; MT) and it is very difficult to diagnose. The symptoms are similar to other infectious neurological diseases, such as neurocysticercosis, neuroborreliosis, or herpes viral infection. The aim of this study was to identify tuberculosis (TB) in cases of meningitis with clinical and laboratory evidence suggestive of TBM, and to confirm our findings with molecular tests for TB infection. We recruited patients with neurological symptoms who were examined at the neurology services of Hospitals of Instituto Mexicano del Seguro Social (IMSS) in Mexico City. A total of 144 consecutive patients with suggestive infectious meningitis were initially included; 94 cases of meningitis with clinical and laboratory evidence suggestive of TBM were included, but only 50 of these cases fulfilled the criteria for probable TBM. As the controls, we included 50 cases of meningitis with clinical and laboratory evidence suggestive of non-TBM. Cerebrospinal fluid (CSF) was collected from all 100 patients (cases and controls) and tested for TB by multiplex and nested PCR analyses. Nested PCR detected 0.1 fg of M. tuberculosis DNA. TB infection was confirmed with molecular tests in 49 patients from the 50 cases suggestive of TBM and in 1 of the 50 non-TBM cases. The analysis exhibited a sensitivity of 98.0%, a specificity of 92.0%, a positive predictive value of 88.0% and a negative predictive value of 98.0%. The use CSF for the analyses proved to be effective for the rapid diagnosis of TBM using a developed system of multiplex and nested PCR analyses in patients presenting neurological symptoms.

Toll-like receptors and cytokines are upregulated during Helicobacter pylori infection in children.

BACKGROUND AND AIM: Helicobacter pylori infection is mainly acquired during childhood, and establishes a chronic infection that may lead to peptic ulcer or gastric cancer during adulthood. Toll-like receptors (TLRs) are expressed by distinct cell types throughout the gastrointestinal tract, and play an important role in regulation of the innate immune response. Few works have addressed TLRs expression in gastric epithelia of adults, and scarce studies have done it in children. The aim of this work was to analyze the expression of TLR2, TLR4, TLR5, TLR9, and IL-8, IL-10 and TNF-α in the gastric mucosa of children with and without H. pylori infection. METHODS: Gastric biopsies were collected by endoscopy from 50 children with recurrent abdominal pain, 25 with H. pylori infection and 25 without infection. In the gastric biopsies the expression of TLRs and cytokines was studied by immunohistochemistry, and the degree of mucosal inflammation was determined using the Sydney system. RESULTS: We found that H. pylori infection was associated with a significant increased expression of TLRs 2, 4, 5 and 9, although expression varied between surface epithelia and glands. Epithelial cells expressing IL-8, IL-10 and TNF-α were increased in gastric mucosa of children with H. pylori infection. CONCLUSION: This study shows the gastric epithelia of children respond to H. pylori infection by increasing the expression of TLR2, TLR4, TLR5, TLR9 and the cytokines IL-8, IL-10 and TNF-α.

Lewis antigen expression by Helicobacter pylori strains colonizing different regions of the stomach of individual patients.

The diversity in the expression of Lewis antigens (Le) of 226 single colonies of Helicobacter pylori isolated from four regions of the stomach of eight adults is shown. Le(y) was expressed more in strains colonizing antrum than in strains colonizing fundus, whereas Le(x) was more common in fundus strains. cagA(+) strains were more associated with Le-negative strains.