Hypothalamic histamine levels in hyperthyroid, arthritic and C48/80-treated rats

Abstract

IntroductionHistamine in the brain is present in at least two cell types: neurons and mast cells (MCs) [1]. Increasing evidence reveals the role of neuronal histamine, but the function of non-neuronal histamine in the brain remains elusive and the association between brain histamine and peripheral physiology is confined to limited reports. Thyroxine treatment has been related to altered MC numbers and histamine levels in the rat brain [2][3]. Without disregarding mast cell heterogeneity, thyroxine T 3 receptors seem to be expressed on rat bone marrow MCs, which change in number depending on thyroid status [4]. However, thyroid hormones were unable to release histamine from peritoneal MCs [2] while, in the rat conjunctiva, hyperthyroidism induced MC structural alteration without parallel disruption of functionality [5]. Additionally, inflammatory mediators [6] and intraperitoneal injection of the selective mast cell degranulator compound 48/80 (C48/80) [7] have been shown to activate brain MCs.This study aimed at determining the hypothalamic histamine content in hyperthyroid and arthritic rats. In an attempt to provide preliminary information regarding the possible connection of non-neuronal histamine to these conditions, the hypothalamic histamine content was determined after systemic administration of C48/80. Materials and methodsMale Wistar rats of 250-300 g were housed under controlled conditions and divided into 5 groups, each subdivided into subgroups A and B. Groups 1A-2A and 3A received a single and 4 daily intraperitoneal doses of 1 mg/kg C48/80 (Sigma), respectively. Hyperthyroidism was induced in group 4A by subcutaneous injection of 0.25 mg/kg L-thyroxine (Sigma), daily for 14 days. The experimental arthritis group 5A received 0.1 ml Freud's adjuvant (Sigma) intradermally into the hind paw. Groups 1B-5B served as controls, being treated with saline accordingly. Groups 1, 2, 3-4 and 5 were sacrificed 2 h, 5 days, 24 h and 14 days after the last dose. The brains were then removed, the hypothalami dissected out and the hypothalamic histamine was quantified fluorometrically [5,8]. The study conformed to local animal laws (license K/4130/02). Inflamm. res. 54, Supplement 1 (2005) S30-S31The results were expressed as the percentage of the histamine content of the respective control and presented as the mean ± SEM. Significant differences were determined using the independent sample t-test and ANOVA. Results and discussionThe hypothalamic histamine content in groups 1B-5B did not differ significantly and ranged from 0.247 ± 0.034 to 0.360 ± 0.031 ng/mg wet tissue (p > 0.05, n = 3-10, ANOVA). Histamine content was significantly lower in hyperthyroid (p < 0.001, n = 9) and arthritic (p < 0.01, n = 10) rats, compared to their control groups (Fig. 1A). Significantly reduced histamine levels were also observed in groups 1A and 3A (p < 0.05 vs. respective control, n = 3-6, Fig. 1B). However, a single C48/80 treatment was unable significantly to alter the amine levels 5 days after administration (p > 0.05, n = 3, Fi...

Time course of thyroxine on hypothalamic histamine in the rat

“…1). This decrease in hypothalamic histamine levels supports the reported T 4 -related decrease in histamine levels [1,2] and in MC numbers [2], however, Upadhyaya and Agrawal showed an elevation of hypothalamic histamine upon T 4 treatment [7].…”

“…Forty-fi ve min after the last dose, the rats were killed and the hypothalami dissected out. Hypothalamic histamine was measured fl uorometrically [1,3]. The study conformed to local animal laws (licence K/4371/03).…”

“…The histamine content of the rat hypothalamus may be affected by chronic thyroxine (T 4 ) treatment in a similar manner to that observed following systemic administration of compound 48/80, a selective mast cell (MC) degranulator [1]. In neonatal rat brains, T 4 treatment altered brain MC numbers but has no effect on neuronal histamine levels nor released histamine from peritoneal MCs [2].…”

Systemic Challenge with Lipopolysaccharide Increases Histamine Levels in the Conjunctiva and Cartilage, but not Hypothalamus of Sprague Dawley rats

“…This indicates that, in male Sprague Dawley rats, systemic challenge with LPS can induce rises in histamine levels in peripheral tissues but not in the hypothalamus. Conversely, challenge with compound 48/ 80, a mast cell degranulator, produces a decrease in tissue histamine levels [4,8]. Therefore, it is likely that the increase in tissue histamine levels seen following challenge with LPS is independent of mast cell degranulation.…”

Blood lymphocyte blastogenesis in patients with thyroid dysfunction: ex vivo response to mitogen activation and cyclosporin A

“…The association between thyroid hormones, immune and neuroendocrine components has been well documented [1][2][3][4]. Thyroid hormones may regulate lymphocyte responsiveness to mitogen-induced proliferation [4] and directly or indirectly influence B and T lymphocyte development through selective microenvironmental actions mediated via TRa thyroid receptors [2].…”