Protection of trinitrobenzene sulfonic acid-induced colitis by an interleukin 2-IgG2b fusion protein in mice.
OBJECTIVE
We have shown in previous studies that an interleukin 2 (IL-2)-IgG2b fusion protein suppresses both humoral and cellular immune reactions 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 immunohistochemistry 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-IgG2b, improvement in both wasting disease and histopathologic signs of colonic inflammation was observed. An increase in the number of colonic CD4(+)/CD25(+) T cells and increased synthesis of the immunosuppressive cytokine IL-10 also occurred. The protective role of IL-10 was demonstrated by the finding that neutralization of IL-10 in vivo using IL-10-specific antibodies inhibited the IL-2-IgG2b effects in TNBS-induced colitis.


CONCLUSIONS
These studies show for the first time that the IL-2-IgG2b fusion protein can abrogate experimental colitis by local induction of IL-10-secreting T cells.
Stallmach
A
A
Institute of Immunology, University of Heidelberg, Heidelberg, Germany. inasta@med-rz.uni-sb.de
Wittig
B
B
Giese
T
T
Pfister
K
K
Hoffmann
J C
JC
Bulfone-Paus
S
S
Kunzendorf
U
U
Meuer
S C
SC
Zeitz
M
M
D000818:Animals; D003092:Colitis / Q000139:chemically induced* / Q000188:drug therapy* / Q000473:pathology / Q000517:prevention & control*; D003106:Colon / Q000473:pathology; D005260:Female; D007074:Immunoglobulin G / Q000235:genetics*; D007376:Interleukin-2 / Q000235:genetics*; D051379:Mice; D008807:Mice, Inbred BALB C; D011993:Recombinant Fusion Proteins / Q000627:therapeutic use*; D014302:Trinitrobenzenesulfonic Acid
D007074:Immunoglobulin G; D007376:Interleukin-2; D011993:Recombinant Fusion Proteins; D014302:Trinitrobenzenesulfonic Acid