title: Serum and gene expression profile of tumor necrosis factor-alpha and interleukin-6 in hypertensive diabetic patients: effect of amlodipine administration.
abstract: Pro-inflammatory cytokines are critical factors in type 2 diabetes-associated atherosclerosis. We aim to analyze in hypertensive type 2 diabetic patients the serum concentrations and the mRNA expression levels in peripheral blood mononuclear cells (PBMC) of the pro-inflammatory cytokine tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6), as well as to evaluate the effect of amlodipine administration. Twenty-one hypertensive diabetic patients and 10 healthy non-diabetic controls were included in the study. Serum levels of cytokines were measured by chemiluminescent immunometric assay, and mRNA expression levels by RT-PCR. The mean serum concentrations of TNF-alpha and IL-6 in diabetic patients showed a 6.1-fold and 2.9-fold increase with respect to non-diabetic control subjects, respectively (p less than 0.0001). Likewise, there was a 3.3- and a 4-fold increase in the PBMC mRNA expression level of TNF-alpha and IL-6 (p less than 0.0001) in diabetic subjects. After amlodipine administration, a significant decrease (p less than 0.01) was observed in the serum TNF-alpha and IL-6 levels. In addition, pre-treatment mRNA expression of TNF-alpha and IL-6 also decreased, with a mean percent reduction of 26 percent (p less than0.01) and 25 percent (p less than 0.001), respectively. In conclusion, serum concentrations and PBMC mRNA expression levels of TNF-alpha and IL-6 are significantly elevated in hypertensive type 2 diabetic patients. Administration of amlodipine is associated with a significant reduction of the increased levels of these inflammatory parameters, both at the protein as well as at the transcriptional level. These modulatory effects of amlodipine on proinflammatory cytokine level and expression may be related to its suggested anti-atherosclerotic actions.
authors.affiliation: Nephrology Service, University Hospital Nuestra Senora de Candelaria, Santa Cruz de Tenerife, Spain. jnavgon@gobiernodecanarias.org
authors.forename: J
authors.initials: J
authors.lastname: Navarro-Gonzalez
authors.forename: C
authors.initials: C
authors.lastname: Mora-Fernandez
authors.forename: M
authors.initials: M
authors.lastname: Gomez-Chinchon
authors.forename: M
authors.initials: M
authors.lastname: Muros
authors.forename: H
authors.initials: H
authors.lastname: Herrera
authors.forename: J
authors.initials: J
authors.lastname: Garcia
mesh_terms: D000368:Aged; D017311:Amlodipine / Q000494:pharmacology*; D000959:Antihypertensive Agents / Q000494:pharmacology*; D050197:Atherosclerosis / Q000209:etiology; D002097:C-Reactive Protein / Q000032:analysis; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000276:immunology*; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D006973:Hypertension / Q000188:drug therapy / Q000276:immunology*; D015850:Interleukin-6 / Q000097:blood* / Q000235:genetics; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000032:analysis; D014409:Tumor Necrosis Factor-alpha / Q000097:blood* / Q000235:genetics
chemical_list: D000959:Antihypertensive Agents; D015850:Interleukin-6; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D017311:Amlodipine; D002097:C-Reactive Protein