TGF-beta1 production in inflammatory bowel disease: differing production patterns in Crohn's disease and ulcerative colitis.
Transforming growth factor-beta (TGF-beta) is an inhibitory cytokine recognized as a key regulator of immunological homeostasis and inflammatory responses. TGF-beta is involved in experimental models of oral tolerance and in the pathogenesis of experimental colitis. Patients with inflammatory bowel disease (IBD) have inappropriate T cell responses to antigenic components of their own intestinal microflora, suggesting the presence of a disorder in the normal mucosal immune mechanism that ensures the down-regulation of responses to harmless constituents in the microflora. To evaluate the contribution of TGF-beta to this imbalance, we measured TGF-beta1 production by lamina propria mononuclear cells (LPMC) and T cells isolated from tissue specimens of patients with Crohn's disease (CD), ulcerative colitis (UC) and controls. Cells were cultured in the presence or absence of anti-CD2 plus anti-CD28 MoAbs and TGF-beta1 production in culture supernatants was measured by ELISA. LPMC isolated from CD patients produced significantly less TGF-beta1 than controls when stimulated via CD2 plus CD28 pathways (P = 0.001)] conversely, in UC patients increased production of TGF-beta1 compared to controls was observed (P = 0.0005). These differences were also observed with purified lamina propria (LP) T cells in both diseases and were associated with the presence of inflammation. Thus, TGF-beta1 production shows contrasting secretion in CD and in UC, probably as a consequence of the different Th polarization. The absolute or relative defect in TGF-beta1 production observed in CD and UC may contribute to the perpetuation of inflammation.
Del Zotto
B
B
Laboratory of Immunology, Istituto Superiore di Sanita', Rome, Italy.
Mumolo
G
G
Pronio
A M
AM
Montesani
C
C
Tersigni
R
R
Boirivant
M
M
D000328:Adult; D000368:Aged; D002478:Cells, Cultured; D003093:Colitis, Ulcerative / Q000276:immunology*; D003424:Crohn Disease / Q000276:immunology*; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D015848:Interleukin-5 / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000378:metabolism*; D008875:Middle Aged; D018709:Statistics, Nonparametric; D013601:T-Lymphocytes / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000276:immunology*
D015848:Interleukin-5; D016212:Transforming Growth Factor beta; D007371:Interferon-gamma