Type 1 T-helper cell predominance in granulomas of Crohn's disease.
OBJECTIVE
The pathogenesis of Crohn's disease (CD) is thought to be associated with production of several cytokines, especially type-1 cytokines. To elucidate the in situ cytokine profiles in CD, cytokine-containing cells were localized by immunohistochemistry, with special attention to noncaseating granulomas. The results were compared with those from studies of ulcerative colitis (UC).


METHODS
We adopted the biotin-streptavidin-peroxidase method on frozen sections obtained at surgery from patients with CD or UC, and we immunohistochemically examined the expression of several cytokines (interferon-gamma, interleukin-2, -4, -10, and -12).


RESULTS
In normal colonic tissue, expression of these cytokines was rare except for interleukin-4. In actively inflamed areas of CD, increased expression of all cytokines by mononuclear cells was observed. In contrast, granulomas in CD involved interferon-gamma+ lymphocytes and interleukin-12+ macrophage-lineage cells (epithelioid cells and multinucleated giant cells) but few interleukin-4+ or -10+ cells. Actively inflamed areas of UC also showed an increase in the number of cytokine-containing cells; however, quantitative analysis revealed that there was more expression of interferon-gamma and interleukin-12, and less of interleukin-10, in CD than in UC, indicating the presence of more type 1 T-helper cells in CD tissue than in UC.


CONCLUSIONS
The findings of the present study suggest that granulomas of CD are coupled with type 1 T-helper responses; these responses may contribute to the pathogenesis of this disease.
Kakazu
T
T
Department of Internal Medicine, University of the Ryukyus, Okinawa, Japan.
Hara
J
J
Matsumoto
T
T
Nakamura
S
S
Oshitani
N
N
Arakawa
T
T
Kitano
A
A
Nakatani
K
K
Kinjo
F
F
Kuroki
T
T
D000328:Adult; D003424:Crohn Disease / Q000276:immunology* / Q000473:pathology; D016207:Cytokines / Q000378:metabolism; D005260:Female; D006099:Granuloma / Q000276:immunology* / Q000473:pathology; D006801:Humans; D007124:Immunoenzyme Techniques; D007413:Intestinal Mucosa / Q000276:immunology / Q000473:pathology; D018655:Lymphocyte Count; D008297:Male; D018417:Th1 Cells / Q000276:immunology* / Q000473:pathology
D016207:Cytokines