Regulation of interleukin-10 secretion by histamine in TH2 cells and splenocytes

Natalia Osna, Kathleen Elliott, Manzoor M. Khan

Research output: Contribution to journalArticlepeer-review

89 Scopus citations


Interleukin-10 is a potent suppressive factor that down-regulates cellular immune response via inhibition of the production of TH1 cytokines. Histamine shifts the TH1/TH2 balance from TH1 to TH2 cytokines making the effects of histamine on IL-10 secretion an important factor in this switch. This study was designed to assess the role of histamine in the regulation of IL-10 production and the involvement of PKA and STAT factors in this process. TH2 cells (D10.G4.1) and AKR/j splenocytes were pretreated with histamine at a concentration range of 10-8-10-5 M for 1 h and then activated with PMA + ionomycin or anti-CD3 for 24 h. The supernatants were collected and tested for IL-10 content by ELISA. Histamine stimulated IL-10 production in TH2 cells in a dose-dependent manner that was reversed by both H1- and H2-receptor antagonists and by PKA inhibitors H8 and Rp-cAMPS. Tyrphostin also reversed the stimulation of IL-10 secretion by histamine, indicating that STAT factors were involved in this process. The up-regulation of IL-10 production by histamine in splenocytes was accompanied by inhibitory effects of histamine on IFNγ production. The pretreatment of splenocytes with histamine in the presence of anti-IL-10 abrogated histamine-mediated inhibition of IFNγ production suggesting that the effects of histamine on IFNγ secretion were regulated by IL-10 in multi-cell system.

Original languageEnglish (US)
Pages (from-to)85-96
Number of pages12
JournalInternational Immunopharmacology
Issue number1
StatePublished - 2001
Externally publishedYes


  • Histamine
  • Interferon gamma
  • Interleukin-10
  • Protein kinase A
  • Splenocytes
  • TH2 cloned cells
  • Tyrphostin

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Pharmacology


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