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

Interleukin-10 is a potent suppressive factor that down-regulates cellular immune response via inhibition of the production of Till cytokines. Histami ne 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 s tudy was designed to assess the role of histamine in the regulation of IL-1 0 production and the involvement of PKA and STAT factors in this process. T H2 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 P MA + ionomycin or anti-CD3 For 24 h. The supernatants were collected and te sted for IL-10 content by ELISA. Histamine stimulated IL-10 production in T H2 cells in a dose-dependent manner that was reversed by both H1- and H2-re ceptor antagonists and by PKA inhibitors H8 and Rp-cAMPS. Tyrphostin also r eversed the stimulation of IL-10 secretion by histamine, indicating that ST AT factors were involved in this process, The up-regulation of IL-10 produc tion by histamine in splenocytes was accompanied by inhibitory effects of h istamine on IFN gamma production. The pretreatment of splenocytes with hist amine in the presence of anti-IL-10 abrogated histamine-mediated inhibition of IFN gamma production suggesting that the effects of histamine on IFN ga mma secretion were regulated by IL-10 in multi-cell system. (C) 2001 Elsevi er Science B.V. All rights reserved.