A new agent for tumour necrosis factor-alpha inhibition: In vitro effects of dipyridamole in Crohn's disease.
BACKGROUND
Tumour necrosis factor-alpha (TNF-alpha) plays a central role in inflammatory cascade in Crohn's disease (CD). Our study aims to investigate the in vitro effects of dipyridamole (DP) on the TNF-alpha and interleukin-10 (IL-10) production in the intestinal mononuclear cells of CD patients.


METHODS
Thirteen patients with CD and in 17 healthy individuals underwent colonoscopy and biopsy samples were taken. Cultured mononuclear cells were preincubated with DP1 (0.7 microg/ml), DP2 (1.25 microg/ml), methotrexate (MTX)1 (0.5 nmol/L) and MTX2 (1.5 nmol/L). These cells were then stimulated with lipopolysaccaride (LPS) and phytohemagglutinin (PHA). The levels of TNF-alpha and IL-10 in supernatants were measured with standard immunoassay monoclonal antibody method.


RESULTS
An appropriate cell culture could be obtained in 10 patients with CD and 12 healthy individuals. In LPS stimulated cells, MTX1 and MTX2 were superior to DP1 and DP2 in suppressing TNF-alpha in both groups. In PHA stimulated cells, while MTX1 was superior to DP1, MTX2 and DP2 had an equivalent effect in CD patients (p<0.05, p>0.05, respectively). In LPS-stimulated cells DP2 was significantly superior to MTX2 in increasing IL-10 levels in both groups (p<0.05). In PHA stimulated cells, DP1 and DP2 caused a higher increase in IL-10 levels compared with MTX1 and MTX2 in CD group (p<0.05).


CONCLUSIONS
Dipyridamole suppresses TNF-alpha similar with MTX. It seems to be superior to MTX in increasing IL-10 levels. Addition of DP to anti-TNF medications may create a synergy in cytokine modulation.
Poturoglu
Sule
S
Department of Internal Medicine, Division of Gastroenterohepatology Istanbul University, Istanbul, Turkey. sulepot@mynet.com
Kaymakoglu
Sabahattin
S
Gurel Polat
Nuray
N
Ibrisim
Duygu
D
Ahishali
Emel
E
Akyuz
Filiz
F
Badur
Selim
S
Demir
Kadir
K
Mungan
Zeynel
Z
D000293:Adolescent; D000328:Adult; D016022:Case-Control Studies; D003424:Crohn Disease / Q000188:drug therapy* / Q000378:metabolism; D004176:Dipyridamole / Q000494:pharmacology* / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D016753:Interleukin-10 / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D008727:Methotrexate / Q000494:pharmacology; D008875:Middle Aged; D010835:Phytohemagglutinins / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors* / Q000378:metabolism; D055815:Young Adult
D008070:Lipopolysaccharides; D010835:Phytohemagglutinins; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D004176:Dipyridamole; D008727:Methotrexate