Interleukin-5 participates in the pathogenesis of ileitis in SAMP1/Yit mice.
SAMP1/Yit mice spontaneously develop ileitis resembling Crohn's disease (CD) without chemical or genetic manipulations. Since the focus of studies were Th1 cytokines, only Th1-type T cells were thought to be responsible for intestinal inflammation in these mice. To further characterize the pathogenesis of this ileitis, we investigated the implication of Th2 cytokines in ileitis of SAMP1/Yit mice. The expression of chemokine receptors (CCR) associated with both Th1 and Th2 lymphocytes, such as CCR2, CCR3, CCR4, CCR5, and CCR8, was increased. Among cytokines, IL-5 was remarkably increased in Peyer's patches, mesenteric lymph nodes, and mucosa involved in ileitis. Furthermore, infiltration of numerous eosinophils in ileitis was histologically evident. Severe combined immunodeficiency mice injected intraperitoneally with CD4(+) cells from SAMP1/Yit mice developed colitis and ileitis, with the infiltration of eosinophils. Administration of anti-IL-5 antibodies significantly attenuated ileitis in these mice. We suggest that IL-5 participates in the pathogenesis of ileitis and that anti-IL-5 antibodies are potentially useful for immunotherapy in CD patients. This is the first demonstration that IL-5 is crucial for the development of ileitis in this mouse model of CD.
Takedatsu
Hidetoshi
H
Second Department of Internal Medicine, Kurume University, Kurume, Fukuoka, Japan.
Mitsuyama
Keiichi
K
Matsumoto
Satoshi
S
Handa
Kazuyo
K
Suzuki
Asuka
A
Takedatsu
Hiroko
H
Funabashi
Hideyuki
H
Okabe
Yoshio
Y
Hara
Taeko
T
Toyonaga
Atsushi
A
Sata
Michio
M
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D003424:Crohn Disease / Q000276:immunology* / Q000473:pathology; D004195:Disease Models, Animal; D004804:Eosinophils / Q000276:immunology*; D005434:Flow Cytometry; D006651:Histocytochemistry; D007079:Ileitis / Q000276:immunology* / Q000473:pathology; D007082:Ileum / Q000276:immunology / Q000473:pathology; D016130:Immunophenotyping; D015848:Interleukin-5 / Q000235:genetics / Q000276:immunology*; D007413:Intestinal Mucosa / Q000276:immunology / Q000473:pathology; D051379:Mice; D016513:Mice, SCID; D012313:RNA / Q000737:chemistry / Q000235:genetics; D019707:Receptors, Chemokine / Q000235:genetics / Q000276:immunology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013047:Specific Pathogen-Free Organisms; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology
D015848:Interleukin-5; D019707:Receptors, Chemokine; D012313:RNA