Histamine regulates T-cell and antibody responses by differential expression of H1 and H2 receptors

Abstract

Many pathological processes, including those causing allergies and autoimmune diseases, are associated with the presence of specialized subsets of T helper cells (TH1 and TH2) at the site of inflammation. The diversity of TH1 and TH2 function is not predetermined but depends on signals that drive the cells towards either subset. Histamine, released from effector cells (mast cells and basophils) during inflammatory reactions can influence immune response. Here we report that histamine enhances TH1-type responses by triggering the histamine receptor type 1 (H1R), whereas both TH1- and TH2-type responses are negatively regulated by H2R through the activation of different biochemical intracellular signals. In mice, deletion of H1R results in suppression of interferon (IFN)-gamma and dominant secretion of TH2 cytokines (interleukin (IL)-4 and IL-13). Mutant mice lacking H2R showed upregulation of both TH1 and TH2 cytokines. Relevant to T-cell cytokine profiles, mice lacking H1R displayed increased specific antibody response with increased immunoglobulin-epsilon (IgE) and IgG1, IgG2b and IgG3 compared with mice lacking H2R. These findings account for an important regulatory mechanism in the control of inflammatory functions through effector-cell-derived histamine.

Modulation of in vivo immunoglobulin production by endogenous histamine and H1R and H2R agonists and antagonists

“…Neither H2R antagonist (ranitidine) nor H3R antagonist/H4R-partial agonist (clobenpropit) had any impact on histamine binding to the Th1 cells. This study demonstrated the expression of H1Rs on Th1 cells and H2Rs on Th2 cells by antibodies generated against the H1R and H2R [6].…”

“…Histamine is a potent agonist of all four receptors (H1-H4) [6,13,14] that are distributed in different parts of body. These receptors modulate different biochemical, pharmacological and immunological reactions, both in vivo and in vitro, by activating signal transduction pathways for endogenous histamine release [13].…”

“…Histamine regulates dendritic cells, T-lymphocytes, B-lymphocytes and related antibody isotype responses. Recently, accumulating evidence has highlighted the importance of histamine receptors in immunomodulation [3,6,8,13]. Histamine can modulate the immune response when it is released from mast cells and basophils during inflammatory reactions [3].…”

“…H1Rs and H2Rs are also regulated by specific cytokines present in the immune system. Jutel et al [6] investigated the H1R-specific antagonist tripelennamine and found that it inhibited histamine binding in T helper (Th) 1 but not in Th2 cells. This study also demonstrated predominant H1R expression on Th1 cells.…”

Cimetidine in colorectal cancer – are the effects immunological or adhesion-mediated?

“…Histamine negatively regulates T helper (T H 1 and T H 2) cell responses through the H 2 receptor and H 2 receptor knockout mice show upregulation of T H 1 and T H 2 cytokines (Jutel et al, 2001). Increased release of histamine has been proposed as the cause of the immunosuppression seen at the time of colonic resection and several studies have shown that perioperative H 2 receptor antagonists can prevent this effect, thereby improving immune surveillance at the time of surgery (Adams et al, 1994b).…”