Soluble lnterleukin-2 Receptor, lnterleukin-6 and Interleukin-1 β in Patients with Crohn’s Disease and Ulcerative Colitis: Preoperative Levels and Postoperative Changes of Serum Concentrations

Abstract

Crohn’s disease (CD) and ulcerative colitis (UC) show an intestinal activation of T cells and macrophages within the inflamed lesions. The aim of the present prospective study was to determine whether circulating interleukins (IL) represent useful markers of immune activation in vivo and to characterize their respective roles in monitoring disease activity. Serum concentrations of the soluble IL-2 receptor (sIL-2R), IL-6 and IL-1 β were measured in 10 patients with CD and 10 patients with UC before, at day 10 and 2 years after resection of inflamed bowel segments. The data were correlated with neopterin, C-reactive protein and other standard parameters of disease activity. Preoperatively, mean sIL-2R concentration was 495 ± 62 U/ml (mean ± SEM; healthy controls: 210 ± 25 U/ml; p < 0.02) in CD and 705 ± 120 U/ml (p < 0.00002) in UC. The corresponding IL-6 serum concentrations were 37 + 6 U/ml in CD (controls: 11 ± 0.6 U/ml; p < 0.0036) and 33 ± 6 U/ml (p < 0.04) in UC. Two years postoperatively, sIL-2R was still elevated in 6 out of 9 patients in both disease groups. These patients did not differ from the remaining group with respect to disease activity. Serum IL-6, elevated in 7 patients with CD and in 6 patients with UC at day 10 postoperatively, had returned to normal in all patients by this time. There was a significant correlation between sIL-2R and neopterin (r = 0.52; p < 0.02) and between IL-6 and C-reactive protein (r = 0.44; p < 0.05) but not between sIL-2R and C-reactive protein. The sensitivity of increased concentrations of sIL-2R and IL-6 to reflect active CD and UC is comparable to that of neopterin and C-reactive protein.

Molecular evidence for two forms of Crohn disease.

“…In this study we used resected intestinal tissue samples. It is conceivable that our identified cytokine differences may be demonstrable in tests on peripheral blood (12,25), thus permitting differentiation between the two clinical forms of CD using a blood test. Should our observations have therapeutic implications (see below), such peripheral blood testing would permit identification of those patients most likely to benefit from such therapy.…”

Effect of Experimental Colitis on Bone Metabolism in the Rat

“…All three cytokines share simi lar actions in vivo, i.e. induction of fever, wasting, leuko cytosis, and hepatic acute-phase protein synthesis, effects which are common features of flare-ups of IBD [34], In Crohn's disease serum IL-6 has been found elevated and it seems to reflect the degree of disease activity [35][36][37], Spontaneous or stimulated release of cytokines from blood monocytes has been found enhanced in Crohn's disease [38,39].…”

Interleukin-6 and soluble interleukin-6 receptor in the colonic mucosa of inflammatory bowel disease

“… 6 In patients with IBD, increased serum concentrations of IL‐6 have been described 7–12 and its assessment may be useful as an indicator of disease activity and response to therapy. 8–10,12 Nevertheless, direct measurement of IL‐6 in the intestinal mucosa is more relevant to clarification of its involvement in the pathogenesis of IBD because alterations of serum IL‐6 concentrations may reflect complicated events, such as entry from the inflamed tissue into the intravascular space 7,13 and clearance from the circulation by the liver. 14 Recently, we and other investigators found that intestinal IL‐6 levels were elevated with an increased number of IL‐6‐producing cells in patients with active lesions of IBD.…”