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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

2003; Oxford University Press; Volume: 15; Issue: 2 Linguagem: Inglês

10.1093/intimm/dxg028

1460-2377

Susumu Nakae, Yutaka Komiyama, Shosaku Narumi, Katsuko Sudo, Reiko Horai, Yoh‐ichi Tagawa, Kenji Sekikawa, Koji Matsushima, Masahide Asano, Yoichiro Iwakura,

Dermatology and Skin Diseases

Contact hypersensitivity (CHS) is a typical inflammatory response against contact allergens. Inflammatory cytokines, including IL‐1 and tumor necrosis factor (TNF)‐α, 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‐α during CHS. CHS induced by 2,4,6‐trinitorochlorobenzene as well as oxazolone was suppressed in both IL‐1α/β–/– and TNF‐α–/– mice. Hapten‐specific T cell activation, as examined by T cell proliferation, OX40 expression and IL‐17 production, was reduced in IL‐1α/β–/– mice, but not in TNF‐α–/– mice, suggesting that IL‐1 but not TNF‐α is required for hapten‐specific T cell priming in the sensitization phase. On the other hand, TNF‐α, induced by IL‐1, was necessary for the induction of local inflammation during the elicitation phase. We also found that the expression of IFN‐γ‐inducible protein 10 (IP‐10) was augmented at the inflammatory site. Although IP‐10 mRNA expression was abrogated in TNF‐α–/– mice, both CHS development and TNF‐α mRNA expression occurred normally in IFN‐γ–/– mice, indicating that the induction of IP‐10 during CHS was primarily controlled by TNF‐α. Interestingly, CHS was suppressed by treatment with anti‐IP‐10 mAb, suggesting a critical role for IP‐10 in CHS. Reduced CHS in TNF‐α–/– mice was reversed by IP‐10 injection during the elicitation phase. Thus, it was shown that the roles for IL‐1 and TNF‐α are different, although both cytokines are crucial for the development of CHS.