Tissue levels of tumor necrosis factor-alpha correlates with grade of inflammation in untreated ulcerative colitis.
OBJECTIVE
The immune characterization of ulcerative colitis (UC) has been unclear and controversial. One possible explanation for the discrepancies between earlier cytokine studies in UC may be the fact that the patients included were on immunosuppressive therapy. Thus, the aim of this study was to determine the tumor necrosis factor-alpha (TNF-alpha) level and T(H)1/T(H)2 cytokine expression (mRNA) profile in patients with untreated UC.


METHODS
Forty-four untreated UC patients, 10 untreated Crohn's disease (CD) patients and 28 healthy controls were included in the study. Colon biopsies were processed for quantitative measurements of TNF-alpha, interleukin (IL)-10, IL-18, IL-4 and interferon-gamma (IFN-gamma) mRNA using real-time polymerase chain reaction (PCR). TNF-alpha expression in T-cell lymphocytes (CD3) and macrophages (CD68) were further characterized by immunohistochemistry (IHC).


RESULTS
Compared with the level in normal controls, the TNF-alpha mRNA level in UC patients was clearly increased, especially in patients with moderate to severe disease. The levels of TNF-alpha mRNA increased in proportion to the UC Disease Activity Index (UCDAI) score in UC patients. Differences were also observed between UC and controls for IFN-gamma IL-18, IL-4 and IL-10. Only minor quantitative differences in cytokines were observed between UC and CD, and they were more or less similar when comparing moderate to severe UC and CD. CD3+ lymphocytes and macrophages in lamina propria from CD and UC lesions showed increased intracellular staining of TNF-alpha.


CONCLUSIONS
TNF-alpha is highly expressed in UC and correlates to the grade of inflammation. The sources of TNF-alpha were observed both in CD3+ lymphocytes and in macrophages. Cytokine expression (mRNA) profiles seem to be similar in patients with moderate to severe UC and CD.
Olsen
Trine
T
Laboratory of Gastroenterology, Institute of Clinical Medicine, University of Tromsø, Tromsø, Norway. Trine.Olsen@fagmed.uit.no
Goll
Rasmus
R
Cui
Guanglin
G
Husebekk
Anne
A
Vonen
Barthold
B
Birketvedt
Grethe Støa
GS
Florholmen
Jon
J
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001706:Biopsy; D003093:Colitis, Ulcerative / Q000276:immunology* / Q000473:pathology*; D003106:Colon / Q000737:chemistry; D005260:Female; D015870:Gene Expression; D006801:Humans; D007249:Inflammation / Q000473:pathology*; D016753:Interleukin-10 / Q000096:biosynthesis; D020382:Interleukin-18 / Q000096:biosynthesis; D015847:Interleukin-4 / Q000096:biosynthesis; D007413:Intestinal Mucosa / Q000276:immunology / Q000473:pathology; D008264:Macrophages / Q000737:chemistry; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000032:analysis; D013601:T-Lymphocytes / Q000737:chemistry; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis*
D020382:Interleukin-18; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D015847:Interleukin-4