Interleukin-6 and soluble interleukin-6 receptor in the colonic mucosa of inflammatory bowel disease.
BACKGROUND
Interleukin-6 (IL-6) has multiple immunological effects on a wide variety of cells and tissues. The expression of IL-6 and IL-6 receptor (IL-6R) may be important to the pathogenesis of inflammatory bowel disease (IBD).


METHODS
In the present study, we examined whether mucosal IL-6 and soluble IL-6R were associated with the pathophysiology of IBD using the colonic mucosal specimens obtained from patients with IBD. Enzyme-linked immunosorbent assay was used to measure the levels of IL-6 and sIL-6R in organ cultures of mucosal tissues and in cell cultures of fractionated mucosal cells as well as in the serum. Expression of IL-6 and IL-6R was analysed by reverse transcription-polymerase chain reaction analysis using freshly isolated lamina propria mononuclear cells (LPMC).


RESULTS
The levels of IL-6 and sIL-6R in organ cultures were substantially elevated in patients with IBD, especially in those with histologically active inflammation. In contrast, considerably higher levels of sIL-6R were detected in patients with other types of colonic inflammation who were included as inflammatory controls, but elevation of IL-6 was less prominent in such patients. The positivity for expression of IL-6 and IL-6R mRNA in LPMC was in parallel with the results obtained in organ cultures. In cell cultures, mucosal macrophages were the main cell type producing both IL-6 and sIL-6R on a per cell basis and other cell fractions including colonic epithelial cells and lymphocytes produced substantially lower amounts of these molecules. The levels of IL-6 and sIL-6R in organ cultures, but not those in the serum, showed a significantly positive correlation with the degree of clinical disease activity in patients with IBD.


CONCLUSIONS
Enhanced IL-6/sIL-6R-mediated immune and inflammatory responses may be implicated, at least partly, in the continuation of intestinal inflammation in patients with IBD.
Hosokawa
T
T
First Department of Internal Medicine, Nagoya University School of Medicine, Japan.
Kusugami
K
K
Ina
K
K
Ando
T
T
Shinoda
M
M
Imada
A
A
Ohsuga
M
M
Sakai
T
T
Matsuura
T
T
Ito
K
K
Kaneshiro
K
K
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015703:Antigens, CD / Q000378:metabolism; D002478:Cells, Cultured; D002648:Child; D003106:Colon / Q000378:metabolism*; D046508:Culture Techniques; D005260:Female; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000097:blood / Q000378:metabolism*; D015850:Interleukin-6 / Q000096:biosynthesis* / Q000097:blood / Q000235:genetics; D007413:Intestinal Mucosa / Q000378:metabolism*; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000096:biosynthesis; D019947:Receptors, Interleukin-6 / Q000096:biosynthesis* / Q000097:blood / Q000235:genetics
D015703:Antigens, CD; D015850:Interleukin-6; D012333:RNA, Messenger; D019947:Receptors, Interleukin-6