Histamine enhances granulocyte-macrophage colony-stimulating factor and interleukin-6 production by human peripheral blood mononuclear cells

Abstract

The effect of histamine on the production of cytokines by subpopulations of mononuclear cells was studied. A 3.5-fold increase in the number of myeloid colony-forming units (CFU-C) was observed when bone marrow cells were cultured in the presence of conditioned medium prepared from nonadherent mononuclear cells cultured with 10(-4) M histamine (CM-histamine) compared with phosphate-buffered saline (CM-PBS). Using ELISA and radioimmunoassay kits, histamine was found to enhance the production of GM-CSF (9.6-fold) and IL-6 (8.2-fold) by mononuclear cells but not by nonadherent cells or large granular lymphocytes. Anti-GM-CSF and anti-IL-6 antibodies markedly blocked cytokine activity in CM-PBS, whereas the blocking effect in CM-histamine was moderate, indicating enhanced GM-CSF and IL-6 activity in CM-histamine. No GM-CSF or IL-6 levels could be detected in CM-histamine or CM-PBS prepared from CD3+, CD4+, or CD8+ lymphocytes. Preincubation of CM-histamine with H1 and H2 receptor antagonists resulted in complete blocking of the histamine-enhanced colony-stimulating activity. We conclude that histamine is able to activate human mononuclear cells to generate cytokines such as GM-CSF and IL-6 via H1 and H2 receptors.

Histamine Induces CD86 Expression and Chemokine Production by Human Immature Dendritic Cells

“…In agreement with data reporting that histamine induces IL-1 and IL-6 production by PBMC (16,17) and IL-6 production by endothelial cells (15), we show that histamine up-regulates the expression of the two proinflammatory cytokines by DC. Moreover, in accordance with data obtained using monocytes/macrophages (18 -21), histamine does not induce TNF-␣ nor IL-12 production by DC.…”

A Novel Pathophysiological Mechanism for Osteoporosis Suggested by an in Vivo Gene Expression Study of Circulating Monocytes

“…Histamine may also have effects on the kidney by decreasing synthesis of calcitriol and leading to consequent secondary hyperparathyroidism (42). Locally, histamine can stimulate osteoclast activity (33) and increase osteoclast number (33), production of granulocyte-macrophage colonystimulating factor and interleukin-6 by mononuclear cells (29,30), and expression of tumor necrosis factor-␣ by monocytes (31), which are important cytokines promoting osteoclastogenesis (48,49). Histamine may also stimulate monocytes to produce MCP-1 (monocyte chemoattractant protein-1) and CCR2 (chemokine receptor-2) (25), two important factors mediating chemotaxis of monocytes (50 -52), thereby increasing monocyte recruitment into bone.…”

“…As shown in Fig. 2, histamine affects bone metabolism at multiple levels, locally in osteoclasts (33), mononuclear cells (29,30), and monocytes (25,31) and systemically in the kidney (42). Although the primary cell type for histamine production is mast cells, they are normally not found in the circulation and thus are probably clinically unimportant for osteoporosis, except in hyperplastic conditions, such as mastocytosis (43)(44)(45).…”

Characterization of Anti-Inflammatory Properties and Evidence for No Sedation Liability for the Novel Antihistamine SUN-1334H

“…In this context, expression of the adhesion molecule VCAM-1 induced by IL-4, alone or together with other cytokines [12], has been associated with relatively selective recruitment of eosinophils and lymphocytes at the sites of allergic inflammation [13]. In vitro studies show that histamine released during the early-phase may act as a stimulatory signal for the production of cytokines and the expression of endothelial adhesion molecules [14, 15]. These effects are dose-dependent and can be affected by H 1 and H 2 receptor antagonists [16].…”