Host: The Japanese Pharmacological Society, The Japanese Society of Clinical Pharmacology
Name : WCP2018 (18th World Congress of Basic and Clinical Pharmacology)
Location : Kyoto
Date : July 01, 2018 - July 06, 2018
Background: IL-19 is a member of the IL-10 family of interleukins and is an immuno-modulatory cytokine produced by the main macrophages. The gastrointestinal tissues of IL-19 knockout (KO) mice show exacerbated experimental colitis mediated by the innate immune system and T cells. There is an increasing focus on the interaction and relationship of IL-19 with the function of T cells. Contact hypersensitivity (CHS) is T cell-mediated cutaneous inflammation. Therefore, we asked whether IL-19 regulates CHS. In this study, we investigated the immunological role of IL-19 in CHS induced by 1-fluoro-2,4-dinitrofluorobenzene (DNFB) as a hapten.
Methods: Balb/c genetic background IL-19 KO mice were used. Mice were sensitized by applying 25 μL of 0.5% DNFB in vehicle solution (acetone: olive oil 3:1, v/v) to shaved abdominal skin. Five days after sensitization, the mice were challenged by painting 20 μL of 0.1% DNFB on their ears. Ear swelling was measured with a micrometer at 24 and 48 hours after the challenge.
Results: IL-19KO mice showed severe ear swelling compared with wild-type (WT) mice at 24 and 48 hours after the DNFB challenge. Ear tissue from IL-19KO mice revealed infiltrated cells and edema at 48 hours after the DNFB challenge. The ears of IL-19KO mice had a high population of Gr-1+ cells. However, the recruitment of macrophages, mast cells, and dendritic cells in the ears of IL-19KO mice were at the same level as those in the ears of WT mice. The exacerbation of the CHS response in IL-19 KO mice correlated with increased levels of IL-17 and IL-6, but no alterations were noted in the production of IFN-gamma and IL-4 in the T cells of the lymph nodes. In addition to the effect on T cell response, IL-19 KO mice increased productions of IL-1beta, IL-12, and TNF-alpha.
Conclusions: These results show that IL-19 suppressed hapten-dependent skin inflammation in the elicitation phase of CHS.