Immunomodulatory effect of cimetidine on the proliferative responses of splenocytes from T. cruzi-infected rats

Abstract

The immunomodulatory effect of cimetidine (CIM), a histamine type-2 receptor antagonist, was evaluated in respect to the blastogenic response to Con A of Wistar Furth (WF) rats infected by the Y strain of Trypanosoma cruzi (T. cruzi). Enhancement of blastogenesis of normal splenocytes was observed at a concentration of 10-3M. However, the splenocytes from infected animals responded to concentrations of CIM ranging from 10-8 to 10-3M. The mitogenic response to Con A of cells from infected animals was restored in the presence of CIM. The results show that CIM modulates the "in vitro" proliferative response of cells from T. cruzi-infected rats and suggest an immunoregulatory role of histamine and/or of cells that express H2 receptors in this infection.

Histamine Type 2 Receptor Expression on Peripheral Blood Regulatory Lymphocytes in Patients with Allergic Rhinitis Treated with Specific Immunotherapy

“…Siegel 7 indicated that dimaprit, a selective H2R agonist, activates suppressor cells and Sato confirmed that histamine through H2R may activate suppressor and cytotoxic lymphocytes in rats. 8 Furthermore, Merwid 9 concluded that histamine may activate suppressor activity of Treg lymphocytes in oncological patients. 9 However, Forward 6 revealed that H2 agonist had little effect on Treg cell function, and H2R antagonist, famotidine, did not block the effects of activated mast cells and histamine-induced inhibition of Treg cells.…”

“…However, there are conflicting data regarding the role of H2Rs in Treg cell functioning, and there is no information on the effect of natural pollen exposure and allergen SIT on the expression of H2R on Treg cells. [6][7][8][9]11 Although Forward 6 showed that H2R stimulation may have little or no effect on Treg cells, other authors revealed that the stimulation of lymphocytes through H2R may enhance their suppressive activity. 9 Furthermore, cimetidine, used as an adjuvant in cancer chemotherapy, 10,11 is believed to act through H2R on Treg cells and shifts the balance toward H1R stimulation that suppress regulatory lymphocytes.…”

“…However, there are conflicting data regarding the role of H2Rs in Treg cell functioning, and there is no information on the effect of natural pollen exposure and allergen SIT on the expression of H2R on Treg cells. 6–9,11…”

Human infection with Trypanosoma cruzi induces parasite antigen-specific cytotoxic T lymphocyte responses.

“…While a strong antibody response contributes to the control of acute parasitemia, a potent type 1 cytokine production and a CD8 ϩ T cell-mediated response are largely responsible for the immune control of tissue parasites (4). That CD8 ϩ T cells are of critical importance in resistance to T. cruzi is supported by their predominance in inflammatory foci of parasitized tissues (5)(6)(7)(8), by the correlation between failure to survive the acute stage of infection, increased tissue parasite loads and an absent inflammatory response in mice made deficient of this T cell subset (9)(10)(11), and by the ability of CD8 ϩ T cells from infected mice to act as cytotxic T lymphocytes (CTL) 1 against T. cruzi -infected cells (12). Recent efforts to elucidate the molecules contributing to such MHC class I-restricted responses have led to the identification of amastigote surface protein (ASP)-1 and ASP-2, two surface proteins on the intracellular amastigote stage (13,14), and trypomastigote surface protein (TSA)-1, a surface antigen on the cell-invasive trypomastigote form (15), as the first bona fide targets of CTL in T. cruzi -infected mice (16,17).…”

The systems biology of infection in animal models bears fruit

“…Among the more recently described functions of histamine are the alteration of cytokine production (11,12), immune cell differentiation (11), lymphocyte responsiveness and regulation (13,14), phagocyte motility (12), and phagocyte killing (11). Consistent with this immune-regulatory role, histamine has been implicated in the host response to several other bacteria, although results vary with infection model.…”