ABSTRACT
BACKGROUND: Calcium channel blockers (CCB) are known to modulate immune reactions, so the present study was performed to examine the effects of various CCBs that have shown different effects on transcription factors and on the production of pro-inflammatory cytokines by human peripheral blood mononuclear cells (PBMC). METHODS AND RESULTS: PBMC from healthy volunteers were isolated by Ficoll-paque density centrifugation. To study the effect of CCBs, the PBMC were stimulated with lipopolysaccharide or concanavalin A. After 24 h of incubation, the supernatants were harvested and the interleukin (IL)-1alpha, -1beta, and -6, tumor necrosis factor (TNF)-alpha, and interferon (IFN)-gamma levels were determined by specific enzyme-linked immunosorbent assay. The production of IL-1alpha and -1beta stimulated with lipopolysaccharide was significantly increased in the presence of amlodipine. In contrast, nifedipine and verapamil suppressed the production of IL-1beta, TNF-alpha, and IFN-gamma. Amlodipine and diltiazem significantly increased production of IL-1alpha stimulated with concanavalin A. Nifedipine inhibited production of IL-1alpha, IL-6, and IFN-gamma. Verapamil suppressed production of IFN-gamma. CONCLUSIONS: Differential modulation of cytokine production was seen with various CCBs, and the suppressive effect of nifedipine was most prominent.
Subject(s)
Amlodipine/pharmacology , Calcium Channel Blockers/pharmacology , Cytokines/metabolism , Leukocytes, Mononuclear/drug effects , Leukocytes, Mononuclear/metabolism , Diltiazem/pharmacology , Humans , In Vitro Techniques , Interferon-gamma/metabolism , Interleukin-1alpha/metabolism , Interleukin-1beta/metabolism , Interleukin-6/metabolism , Leukocytes, Mononuclear/cytology , Lipopolysaccharides/pharmacology , Nifedipine/pharmacology , Tumor Necrosis Factor-alpha/metabolism , Verapamil/pharmacologyABSTRACT
BACKGROUND AND AIMS: It has been suggested that the incidence of digestive diseases associated with Helicobacter pylori is influenced by the strain diversity of H. pylori, factors involving the host or environment, and the duration of infection. The authors have previously reported that human leukocyte antigen (HLA)-DQB1*0401 plays an important role in the development of atrophic gastritis in H. pylori infected patients. The aim of the present study was to investigate the relationship between HLA-DQB1 genotype and cancer development. METHODS: HLA-DQB1 genotyping was performed by the PCR-RFLP method on 122 H. pylori-infected non-ulcer dyspepsia (NUD) patients, 53 gastric cancer patients and 28 uninfected controls. To reliably estimate the grade of atrophic gastritis, histological evaluation was performed. RESULTS: The allele frequency of DQB1*0401 was significantly higher in intestinal type cancer patients compared with age- and sex-matched H. pylori-infected NUD patients. There was no significant difference in the mean atrophic scores of the biopsy samples from the lesser curvature of the mid-corpus between these groups. CONCLUSIONS: HLA-DQB1*0401 is a useful marker for determining susceptibility to intestinal type gastric cancer.
