title: Reduced intestinal inflammation induced by dextran sodium sulfate in interleukin-6-deficient mice.
abstract: Interleukin-6 (IL-6) is a multifunctional cytokine secreted by various cells, and is involved in the acute phase response and the immune response through T and B cell activation. To further define the role of IL-6 in intestinal inflammation, we studied the effects of dextran sulfate sodium (DSS) administration in mice with targeted deletions of the IL-6 gene. Acute colitis was induced in female IL-6-/- and IL-6+/+ mice by giving 4.5% DSS orally in drinking water for 8 days. The colonic mucosal injury and inflammation was evaluated based on survival rate, body-weight changes, total colon length and histological findings. Colonic mRNA expression for tumor necrosis factor (TNF)-alpha, IL-6, IL-10 and inducible nitric oxide synthase (iNOS) was measured by RT-PCR. Colonic IL-6 mRNA levels of wild-type mice continued to increase throughout the study period. At each assessment, colonic injury was significantly attenuated in DSS-treated IL-6-/- mice compared with DSS-treated IL-6+/+ mice. Histological study also showed a reduced infiltration of inflammatory cells, especially neutrophils, and mucosal cell disruption in DSS-treated IL-6-/- mice compared with DSS-treated IL-6+/+ mice. In the colons of DSS-treated IL-6-/- mice, the expression of both TNF-alpha mRNA and iNOS mRNA was reduced on day 5. In contrast, IL-10 mRNA expression was enhanced compared with DSS-treated IL-6+/+ mice. In conclusion, DSS-induced inflammation appears to be significantly inhibited in IL-6-/- mice compared to wild-type mice. These data suggest that persistent and marked blockade of IL-6 bioactivity provides some beneficial effects on intestinal inflammation.
authors.affiliation: Molecular Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto 602-8566, Japan. ynaito@koto.kpu-m.ac.jp
authors.forename: Yuji
authors.initials: Y
authors.lastname: Naito
authors.forename: Tomohisa
authors.initials: T
authors.lastname: Takagi
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Uchiyama
authors.forename: Masaaki
authors.initials: M
authors.lastname: Kuroda
authors.forename: Satoshi
authors.initials: S
authors.lastname: Kokura
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Ichikawa
authors.forename: Rie
authors.initials: R
authors.lastname: Yanagisawa
authors.forename: Ken-Ichiro
authors.initials: K
authors.lastname: Inoue
authors.forename: Hirohisa
authors.initials: H
authors.lastname: Takano
authors.forename: Masahiko
authors.initials: M
authors.lastname: Satoh
authors.forename: Norimasa
authors.initials: N
authors.lastname: Yoshida
authors.forename: Takeshi
authors.initials: T
authors.lastname: Okanoue
authors.forename: Toshikazu
authors.initials: T
authors.lastname: Yoshikawa
mesh_terms: D000818:Animals; D000925:Anticoagulants / Q000494:pharmacology; D001402:B-Lymphocytes / Q000276:immunology; D001835:Body Weight / Q000187:drug effects; D003106:Colon / Q000473:pathology; D016207:Cytokines / Q000378:metabolism; D016264:Dextran Sulfate / Q000494:pharmacology*; D017353:Gene Deletion; D007249:Inflammation / Q000139:chemically induced*; D016753:Interleukin-10 / Q000378:metabolism; D015850:Interleukin-6 / Q000235:genetics* / Q000502:physiology*; D007422:Intestines / Q000276:immunology / Q000473:pathology*; D051379:Mice; D008822:Mice, Transgenic; D009092:Mucous Membrane / Q000473:pathology; D009504:Neutrophils / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000276:immunology; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D000925:Anticoagulants; D016207:Cytokines; D015850:Interleukin-6; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D016264:Dextran Sulfate; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse