A. Stallmach et al., Protection of trinitrobenzene sulfonic acid-induced colitis by an interleukin 2-IgG2b fusion protein in mice, GASTROENTY, 117(4), 1999, pp. 866-876
Background & Aims: We have shown in previous studies that an interleukin 2
(IL-2)-IgG2b fusion protein suppresses both humoral and cellular immune rea
ctions in a murine model of DTH reaction. We now analyze the effects of IL-
2-IgG2b in a model of intestinal inflammation in mice induced by the hapten
reagent 2,4,6-trinitrobenzene sulfonic acid (TNBS) that mimics immunologic
characteristics of human Crohn's disease. Methods: In TNBS-induced colitis
, colonic and splenic T-cell subsets were characterized by immunohistochemi
stry and flow cytometry. Cytokine synthesis was studied by semiquantitative
reverse-transcription polymerase chain reaction and intracellular cytokine
staining in CD4(+) T cells. Results: When mice were treated with IL-2-IgG2
b, improvement in both wasting disease and histopathologic signs of colonic
inflammation was observed. An increase in the number of colonic CD4(+)/CD2
5(+) T cells and increased synthesis of the immunosuppressive cytokine IL-1
0 also occurred. The protective role of IL-10 was demonstrated by the findi
ng that neutralization of IL-10 in vivo using IL-10-specific antibodies inh
ibited the IL-2-IgG2b effects in TNBS-induced colitis. Conclusions: These s
tudies show for the first time that the IL-2-IgG2b fusion protein can abrog
ate experimental colitis by local induction of IL-10-secreting T cells.