title: IL-1-induced tumor necrosis factor-alpha elicits inflammatory cell infiltration in the skin by inducing IFN-gamma-inducible protein 10 in the elicitation phase of the contact hypersensitivity response.
abstract: Contact hypersensitivity (CHS) is a typical inflammatory response against contact allergens. Inflammatory cytokines, including IL-1 and tumor necrosis factor (TNF)-alpha, are implicated in the reaction, although the precise roles of each cytokine have not been completely elucidated. In this report, we dissected the functional roles of IL-1 and TNF-alpha during CHS. CHS induced by 2,4,6-trinitorochlorobenzene as well as oxazolone was suppressed in both IL-1alpha/beta(-/-) and TNF-alpha(-/-) mice. Hapten-specific T cell activation, as examined by T cell proliferation, OX40 expression and IL-17 production, was reduced in IL-1alpha/beta(-/-) mice, but not in TNF-alpha(-/-) mice, suggesting that IL-1 but not TNF-alpha is required for hapten-specific T cell priming in the sensitization phase. On the other hand, TNF-alpha, induced by IL-1, was necessary for the induction of local inflammation during the elicitation phase. We also found that the expression of IFN-gamma-inducible protein 10 (IP-10) was augmented at the inflammatory site. Although IP-10 mRNA expression was abrogated in TNF-alpha(-/-) mice, both CHS development and TNF-alpha mRNA expression occurred normally in IFN-gamma(-/-) mice, indicating that the induction of IP-10 during CHS was primarily controlled by TNF-alpha. Interestingly, CHS was suppressed by treatment with anti-IP-10 mAb, suggesting a critical role for IP-10 in CHS. Reduced CHS in TNF-alpha(-/-) mice was reversed by IP-10 injection during the elicitation phase. Thus, it was shown that the roles for IL-1 and TNF-alpha are different, although both cytokines are crucial for the development of CHS.
authors.affiliation: Center for Experimental Medicine, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan.
authors.forename: Susumu
authors.initials: S
authors.lastname: Nakae
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Komiyama
authors.forename: Shosaku
authors.initials: S
authors.lastname: Narumi
authors.forename: Katsuko
authors.initials: K
authors.lastname: Sudo
authors.forename: Reiko
authors.initials: R
authors.lastname: Horai
authors.forename: Yoh-Ichi
authors.initials: Y
authors.lastname: Tagawa
authors.forename: Kenji
authors.initials: K
authors.lastname: Sekikawa
authors.forename: Koji
authors.initials: K
authors.lastname: Matsushima
authors.forename: Masahide
authors.initials: M
authors.lastname: Asano
authors.forename: Yoichiro
authors.initials: Y
authors.lastname: Iwakura
mesh_terms: D000818:Animals; D002465:Cell Movement / Q000502:physiology; D054357:Chemokine CXCL10; D019743:Chemokines, CXC / Q000378:metabolism*; D003877:Dermatitis, Contact / Q000378:metabolism*; D007249:Inflammation / Q000378:metabolism*; D007371:Interferon-gamma / Q000378:metabolism; D007375:Interleukin-1 / Q000378:metabolism*; D007801:Langerhans Cells / Q000378:metabolism; D051379:Mice; D012867:Skin / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
chemical_list: D054357:Chemokine CXCL10; D019743:Chemokines, CXC; D007375:Interleukin-1; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma