Suppression of IFN-γ production in murine splenocytes by histamine receptor antagonists

Miho Kamei, Yukie Otani, Hidenori Hayashi, Tadaho Nakamura, Kazuhiko Yanai, Kazuyuki Furuta, Satoshi Tanaka

Research output: Contribution to journalArticle


Accumulating evidence suggests that histamine synthesis induced in several types of tumor tissues modulates tumor immunity. We found that a transient histamine synthesis was induced in CD11b + Gr-1 + splenocytes derived from BALB/c mice transplanted with a syngeneic colon carcinoma, CT-26, when they were co-cultured with CT-26 cells. Significant levels of IFN-γ were produced under this co-culture condition. We explored the modulatory roles of histamine on IFN-γ production and found that several histamine receptor antagonists, such as pyrilamine, diphenhydramine, JNJ7777120, and thioperamide, could significantly suppress IFN-γ production. However, suppression of IFN-γ production by these antagonists was also found when splenocytes were derived from the Hdc −/− BALB/c mice. Suppressive effects of these antagonists were found on IFN-γ production induced by concanavalin A or the combination of an anti-CD3 antibody and an anti-CD28 antibody in a histamine-independent manner. Murine splenocytes were found to express H 1 and H 2 receptors, but not H 3 and H 4 receptors. IFN-γ production in the Hh1r −/− splenocytes induced by the combination of an anti-CD3 antibody and an anti-CD28 antibody was significantly suppressed by these antagonists. These findings suggest that pyrilamine, diphenhydramine, JNJ7777120, and thioperamide can suppress IFN-γ production in activated splenocytes in a histamine-independent manner.

Original languageEnglish
Article number4083
JournalInternational journal of molecular sciences
Issue number12
Publication statusPublished - Jan 1 2018



  • Histamine
  • Histamine H receptor
  • Histidine decarboxylase
  • IFN-γ
  • Splenocyte

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

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