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Disruption of the suprachiasmatic nucleus blunts a time of day-dependent variation in systemic anaphylactic reaction in mice.

Nakamura Y, Ishimaru K, Tahara Y, Shibata S, Nakao A - J Immunol Res (2014)

Bottom Line: In mammals, the central clock located in the suprachiasmatic nucleus (SCN) of the hypothalamus synchronizes and entrains peripheral circadian clock present in virtually all cell types via neural and endocrine pathways, thereby driving the daily rhythms in behavior and physiology.We found that mechanical disruption of the SCN resulted in the absence of a time of day-dependent variation in passive systemic anaphylactic (PSA) reaction in mice, associated with loss of daily variations in serum histamine, MCP-1 (CCL2), and IL-6 levels.These results suggest that the central SCN clock controls the time of day-dependent variation in IgE-mediated systemic anaphylactic reaction, which may provide a novel insight into the pathophysiology of anaphylaxis.

View Article: PubMed Central - PubMed

Affiliation: Department of Immunology, Faculty of Medicine, University of Yamanashi, 1110 Shimokato, Chuo, Yamanashi 409-3898, Japan.

ABSTRACT
Anaphylaxis is a severe systemic allergic reaction which is rapid in onset and potentially fatal, caused by excessive release of mediators including histamine and cytokines/chemokines from mast cells and basophils upon allergen/IgE stimulation. Increased prevalence of anaphylaxis in industrialized countries requires urgent needs for better understanding of anaphylaxis. However, the pathophysiology of the disease is not fully understood. Here we report that the circadian clock may be an important regulator of anaphylaxis. In mammals, the central clock located in the suprachiasmatic nucleus (SCN) of the hypothalamus synchronizes and entrains peripheral circadian clock present in virtually all cell types via neural and endocrine pathways, thereby driving the daily rhythms in behavior and physiology. We found that mechanical disruption of the SCN resulted in the absence of a time of day-dependent variation in passive systemic anaphylactic (PSA) reaction in mice, associated with loss of daily variations in serum histamine, MCP-1 (CCL2), and IL-6 levels. These results suggest that the central SCN clock controls the time of day-dependent variation in IgE-mediated systemic anaphylactic reaction, which may provide a novel insight into the pathophysiology of anaphylaxis.

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The SCN ablation blunts a time of day-dependent variation in PSA reaction. (a) Changes in rectal temperature over time after the allergen challenge at ZT4 (10:00 a.m.) and ZT16 (10:00 p.m.) in sham-operated mice (Sham) and mice with disrupted SCN (SCND) (n = 4). The arrows indicate the time of antigen challenge (b)–(d). The serum histamine (b), MCP-1 (CCL2) (c), and IL-6 (d) levels following induction of PSA reactions at ZT4 and ZT16 in sham-operated mice or mice with SCN disruption (n = 4 per group). Concentrations of histamine were measured using serum samples collected at 10 and 180 minutes after induction of PSA reaction at ZT4 or ZT10. Concentrations of MCP-1 and IL-6 were measured using serum samples collected at 180 minutes after induction of PSA reaction at ZT4 or ZT16. (e) The serum corticosterone levels at ZT4 and ZT16 in sham-operated mice and mice with SCN disruption (n = 4 per group). *P < 0.05. Similar results were obtained in at least two independent experiments.
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fig2: The SCN ablation blunts a time of day-dependent variation in PSA reaction. (a) Changes in rectal temperature over time after the allergen challenge at ZT4 (10:00 a.m.) and ZT16 (10:00 p.m.) in sham-operated mice (Sham) and mice with disrupted SCN (SCND) (n = 4). The arrows indicate the time of antigen challenge (b)–(d). The serum histamine (b), MCP-1 (CCL2) (c), and IL-6 (d) levels following induction of PSA reactions at ZT4 and ZT16 in sham-operated mice or mice with SCN disruption (n = 4 per group). Concentrations of histamine were measured using serum samples collected at 10 and 180 minutes after induction of PSA reaction at ZT4 or ZT10. Concentrations of MCP-1 and IL-6 were measured using serum samples collected at 180 minutes after induction of PSA reaction at ZT4 or ZT16. (e) The serum corticosterone levels at ZT4 and ZT16 in sham-operated mice and mice with SCN disruption (n = 4 per group). *P < 0.05. Similar results were obtained in at least two independent experiments.

Mentions: The kinetics of PSA reaction was then compared in sham-operated mice and mice with disrupted SCN (Figure 2(a)). Sham-operated mice challenged with the antigen at 10:00 pm (ZT16) showed a smaller drop in the extent of rectal temperatures than the mice challenged at 10:00 am (ZT4). However, such a time of day-dependent variation in PSA reaction was absent in mice with disrupted SCN. Consistently, serum histamine, MCP-1 (CCL2), and IL-6 levels following the induction of the PSA reactions showed similar time of day-dependent variations to the PSA reactions in sham-operated mice, but the variations were absent in mice with disrupted SCN (Figures 2(b)–2(d)). The daily variations in serum corticosterone levels observed in sham-operated mice were also absent in mice with disrupted SCN (Figure 2(e)). In contrast, serum total IgE levels were comparable between sham-operated mice and mice with disrupted SCN (data not shown). These results indicated that disruption of the central clock SCN blunted a time of a day-dependent variation in PSA reaction in association with a loss of rhythmic secretion of corticosterone. These findings suggest that the circadian clock system may contribute to the generation of daily rhythms in anaphylaxis.


Disruption of the suprachiasmatic nucleus blunts a time of day-dependent variation in systemic anaphylactic reaction in mice.

Nakamura Y, Ishimaru K, Tahara Y, Shibata S, Nakao A - J Immunol Res (2014)

The SCN ablation blunts a time of day-dependent variation in PSA reaction. (a) Changes in rectal temperature over time after the allergen challenge at ZT4 (10:00 a.m.) and ZT16 (10:00 p.m.) in sham-operated mice (Sham) and mice with disrupted SCN (SCND) (n = 4). The arrows indicate the time of antigen challenge (b)–(d). The serum histamine (b), MCP-1 (CCL2) (c), and IL-6 (d) levels following induction of PSA reactions at ZT4 and ZT16 in sham-operated mice or mice with SCN disruption (n = 4 per group). Concentrations of histamine were measured using serum samples collected at 10 and 180 minutes after induction of PSA reaction at ZT4 or ZT10. Concentrations of MCP-1 and IL-6 were measured using serum samples collected at 180 minutes after induction of PSA reaction at ZT4 or ZT16. (e) The serum corticosterone levels at ZT4 and ZT16 in sham-operated mice and mice with SCN disruption (n = 4 per group). *P < 0.05. Similar results were obtained in at least two independent experiments.
© Copyright Policy - open-access
Related In: Results  -  Collection

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fig2: The SCN ablation blunts a time of day-dependent variation in PSA reaction. (a) Changes in rectal temperature over time after the allergen challenge at ZT4 (10:00 a.m.) and ZT16 (10:00 p.m.) in sham-operated mice (Sham) and mice with disrupted SCN (SCND) (n = 4). The arrows indicate the time of antigen challenge (b)–(d). The serum histamine (b), MCP-1 (CCL2) (c), and IL-6 (d) levels following induction of PSA reactions at ZT4 and ZT16 in sham-operated mice or mice with SCN disruption (n = 4 per group). Concentrations of histamine were measured using serum samples collected at 10 and 180 minutes after induction of PSA reaction at ZT4 or ZT10. Concentrations of MCP-1 and IL-6 were measured using serum samples collected at 180 minutes after induction of PSA reaction at ZT4 or ZT16. (e) The serum corticosterone levels at ZT4 and ZT16 in sham-operated mice and mice with SCN disruption (n = 4 per group). *P < 0.05. Similar results were obtained in at least two independent experiments.
Mentions: The kinetics of PSA reaction was then compared in sham-operated mice and mice with disrupted SCN (Figure 2(a)). Sham-operated mice challenged with the antigen at 10:00 pm (ZT16) showed a smaller drop in the extent of rectal temperatures than the mice challenged at 10:00 am (ZT4). However, such a time of day-dependent variation in PSA reaction was absent in mice with disrupted SCN. Consistently, serum histamine, MCP-1 (CCL2), and IL-6 levels following the induction of the PSA reactions showed similar time of day-dependent variations to the PSA reactions in sham-operated mice, but the variations were absent in mice with disrupted SCN (Figures 2(b)–2(d)). The daily variations in serum corticosterone levels observed in sham-operated mice were also absent in mice with disrupted SCN (Figure 2(e)). In contrast, serum total IgE levels were comparable between sham-operated mice and mice with disrupted SCN (data not shown). These results indicated that disruption of the central clock SCN blunted a time of a day-dependent variation in PSA reaction in association with a loss of rhythmic secretion of corticosterone. These findings suggest that the circadian clock system may contribute to the generation of daily rhythms in anaphylaxis.

Bottom Line: In mammals, the central clock located in the suprachiasmatic nucleus (SCN) of the hypothalamus synchronizes and entrains peripheral circadian clock present in virtually all cell types via neural and endocrine pathways, thereby driving the daily rhythms in behavior and physiology.We found that mechanical disruption of the SCN resulted in the absence of a time of day-dependent variation in passive systemic anaphylactic (PSA) reaction in mice, associated with loss of daily variations in serum histamine, MCP-1 (CCL2), and IL-6 levels.These results suggest that the central SCN clock controls the time of day-dependent variation in IgE-mediated systemic anaphylactic reaction, which may provide a novel insight into the pathophysiology of anaphylaxis.

View Article: PubMed Central - PubMed

Affiliation: Department of Immunology, Faculty of Medicine, University of Yamanashi, 1110 Shimokato, Chuo, Yamanashi 409-3898, Japan.

ABSTRACT
Anaphylaxis is a severe systemic allergic reaction which is rapid in onset and potentially fatal, caused by excessive release of mediators including histamine and cytokines/chemokines from mast cells and basophils upon allergen/IgE stimulation. Increased prevalence of anaphylaxis in industrialized countries requires urgent needs for better understanding of anaphylaxis. However, the pathophysiology of the disease is not fully understood. Here we report that the circadian clock may be an important regulator of anaphylaxis. In mammals, the central clock located in the suprachiasmatic nucleus (SCN) of the hypothalamus synchronizes and entrains peripheral circadian clock present in virtually all cell types via neural and endocrine pathways, thereby driving the daily rhythms in behavior and physiology. We found that mechanical disruption of the SCN resulted in the absence of a time of day-dependent variation in passive systemic anaphylactic (PSA) reaction in mice, associated with loss of daily variations in serum histamine, MCP-1 (CCL2), and IL-6 levels. These results suggest that the central SCN clock controls the time of day-dependent variation in IgE-mediated systemic anaphylactic reaction, which may provide a novel insight into the pathophysiology of anaphylaxis.

Show MeSH
Related in: MedlinePlus