Activation of monocytes during inflammatory bowel disease.
Inflammatory bowel diseases lead to a systemic acute-phase response. Monocyte activation plays a central role during systemic acute-phase response via secretion of inflammatory cytokines. We determined the activation of peripheral-blood monocytes in patients with inflammatory bowel diseases by measuring their interleukin-6 (IL-6) secretion. Blood was obtained from patients with active Crohn's disease before treatment [mean Crohn's disease activity index (CDAI) = 332 +/- 34] and from patients after treatment with prednisolone (mean CDAI index = 139 +/- 20). The mean serum IL-6 levels measured by a hybridoma growth assay (B9) were 23 +/- 4 U/ml before therapy and fell to 16 +/- 3 U/ml after treatment with prednisolone. Healthy persons and patients with inactive Crohn's disease usually had serum IL-6 levels below the detection limit of 4 U/ml. An ex vivo whole-blood system was used to measure IL-6 secretion by peripheral-blood monocytes with and without stimulation. Spontaneous IL-6 secretion in this system was about 9 U/ml in patients with Crohn's disease and below the detection limit of 4 U/ml in healthy controls. Moderate stimulation of blood cells [100 pg/ml lipopolysaccharide (LPS)] from patients with active Crohn's disease before and after treatment led to mean IL-6 concentrations of 1,160 +/- 514 and 131 +/- 54 U/ml, respectively. Maximal stimulation of peripheral blood before and after therapy by LPS (100 ng/ml) led to mean IL-6 concentrations of 5,570 +/- 1,660 and 6,220 +/- 1,630 U/ml, respectively. Thus, administration of glucocorticoids led to a rapid down-regulation of IL-6 synthesis by peripheral-blood monocytes.(ABSTRACT TRUNCATED AT 250 WORDS)
Andus
T
T
Abteilung für Gastroenterologie, Medizinische Universitätsklinik Freiburg, BRD.
Gross
V
V
Cäsar
I
I
Krumm
D
D
Hosp
J
J
David
M
M
Schölmerich
J
J
D000209:Acute-Phase Proteins / Q000096:biosynthesis; D000210:Acute-Phase Reaction / Q000209:etiology; D003424:Crohn Disease / Q000188:drug therapy / Q000209:etiology / Q000276:immunology*; D005938:Glucocorticoids / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D015850:Interleukin-6 / Q000097:blood / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D009000:Monocytes / Q000276:immunology*
D000209:Acute-Phase Proteins; D005938:Glucocorticoids; D015850:Interleukin-6; D008070:Lipopolysaccharides