Peripheral blood monocyte cytokine production and acute phase response in inflammatory bowel disease

Abstract

Cytokines released from activated mononuclear leukocytes are involved in triggering the acute phase response and many of the inflammatory manifestations of ulcerative colitis and Crohn's disease. The ability of circulating monocytes from patients with ulcerative colitis and Crohn's disease to generate the cytokines interleukin 1 beta (IL 1 beta) and tumour necrosis factor alpha (TNF alpha), both spontaneously and in response to stimulation by lipopolysaccharide, was compared. IL 1 beta generation in response to lipopolysaccharide was significantly higher in Crohn's disease than in ulcerative colitis and normal controls, with a dramatic increase in patients with active disease. There was a significant reduction in lipopolysaccharide stimulated TNF alpha generation in ulcerative colitis patients compared with Crohn's disease and normal control subjects. IL 1 beta and TNF alpha release correlated significantly with serum C reactive protein and serum alpha 1 acid glycoprotein in Crohn's disease. The ability of conditioned medium from monocytes in Crohn's disease to enhance release of alpha 1 acid glycoprotein from the liver cell line HepG2 in culture was assessed. There was a significant positive correlation between TNF alpha and IL 1 beta presence in the supernatant and alpha 1 acid glycoprotein production. The differences in the cytokine profile in patients with Crohn's disease compared with ulcerative colitis suggest an intrinsic difference in the ability to produce cytokines in patients with these two forms of inflammatory bowel disease, and may explain features such as the enhanced ability to generate a brisk C reactive protein response in Crohn's disease.