Circulating monocytes and plasma inflammatory biomarkers in active Crohn's disease: elevated oxidized low-density lipoprotein and the anti-inflammatory effect of atorvastatin.
We investigated inflammatory biomarkers in plasma and in circulating monocytes obtained from patients with Crohn's disease and healthy individuals. Additionally, we assessed the effects of atorvastatin, 10 microM, ex vivo on monocytes cultured for 18 hours from the same subjects. Plasma and blood monocytes from eight patients with active Crohn's disease and eight healthy individuals were analyzed by enzyme-linked immunosorbent and electrophoretic mobility assays. Patients with active Crohn's disease had increased plasma levels of tumor necrosis factor (TNF)-alpha (7.7-fold;p < 0.05), monocyte chemoattractant protein (MCP)-1 (1.3-fold; p < 0.05), and oxidized low density lipoprotein (oxLDL) (1.2-fold; p < 0.05). Monocytes from patients with Crohn's disease showed enhanced secretion of MCP-1 (4.8-fold; p < 0.05) and a markedly suppressed secretion of macrophage migration inhibitory factor (MIF) (93%; p < 0.001). Transcriptional activation of nuclear factor-kappaB did not differ between the groups. Treating monocytes with atorvastatin resulted in the suppression of MCP-1 (42%; p < 0.05) and TNF-alpha (45%; p < 0.05) secretion. These results show increased levels of certain proinflammatory biomarkers, including oxLDL, in plasma and indicate that peripheral blood monocytes in active Crohn's disease are sensitized to chemotaxis. Treatment with atorvastatin may be a potential strategy to reduce oxLDL and inhibit monocyte migration to inflamed tissue, thus attenuating the inflammatory response.
Gastroenterology and Hepatology Division, Department of Medicine, Lund University, Malmö University Hospital, Malmö, Sweden. olof.grip@medforsk.mas.lu.se
Olof
O
Grip
Sabina
S
Janciauskiene
Stefan
S
Lindgren
D000293:Adolescent; D000328:Adult; D000069059:Atorvastatin; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D018932:Chemokine CCL2 / Q000097:blood; D003424:Crohn Disease / Q000097:blood*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006538:Heptanoic Acids / Q000494:pharmacology*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D008077:Lipoproteins, LDL / Q000097:blood* / Q000187:drug effects*; D008263:Macrophage Migration-Inhibitory Factors / Q000097:blood; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000187:drug effects* / Q000378:metabolism; D011758:Pyrroles / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D015415:Biomarkers; D018932:Chemokine CCL2; D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D008077:Lipoproteins, LDL; D008263:Macrophage Migration-Inhibitory Factors; D011758:Pyrroles; D014409:Tumor Necrosis Factor-alpha; C099252:oxidized low density lipoprotein; D000069059:Atorvastatin