To explore the impact of seasonal changes on the T-helper 1 (Th1)/T-helper 2 (Th2) immune balance of the body in order to elucidate the internal immunological mechanisms underlying seasonal eczema.

Eighty 4-week-old male Sprague–Dawley rats were divided into 5 season groups kept in corresponding season simulation environments, and subdivided into the model group and the control group. The Eczema Area and Severity Index (EASI) and scratching frequency were evaluated. The serum levels of immunoglobulin E (IgE), interleukin-2 (IL-2), interleukin-12 (IL-12), and interferon-gamma (IFN-γ), interleukin-4 (IL-4), interleukin-25 (IL-25), and interleukin-31 (IL-31), and melatonin (MT), as well as the MT receptor (MTR) levels in the spleen, were detected by enzyme-linked immunosorbent assay analysis. The mRNA expression levels of T-bet and GATA3 were detected by quantitative real-time polymerase chain reaction.

EASI scores and the scratching frequency of the model group were higher in the long summer than in the other 4 seasons. Meanwhile, the serum levels of IgE and the Th2 cytokines IL-4, IL-25, and IL-31, as well as GATA3 mRNA expression levels, were high during the long summer in both groups. However, the serum levels of the Th1 cytokines IL-2, IL-12, and IFN-γ, as well as MT, MTR, and T-bet mRNA levels, were lower during the long summer. In all 5 seasonal groups (spring, summer, long summer, autumn, and winter), the levels of all immune factors, especially IL-4 and IL-31, were higher in the model group than those in the control group, while the concentrations of MT and MTR were lower.

Under long light, hot, and humid conditions in the long summer, the body is more likely to suffer from Th2-dominated immune imbalance. This is the internal mechanism behind the high incidence and severity of eczema during the long summer. MT and MTR play a key role in the seasonal onset of eczema.

Based on the effect of seasonal changes on human visceral function, this study investigated the impact of seasonal photoperiod of the pineal body on hypothalamic-pituitary-adrenal axis-hippocampal-receptor in rats, aiming to reveal the mechanism by which pineal gland melatonin regulates the seasonal secretion of hippocampal neurotransmitters.

Vernal equinox, summer solstice, autumn equinox, and winter solstice were selected as four experimental time points, and rats were randomly divided into normal control group, sham operation group, and pinealectomized group. The seasonal changes in corticotropin-releasing hormone (CRH), adrenocorticotropic hormone (ACTH), corticosterone, hypothalamic melatonin receptor (MTR), and hippocampal corticosterone receptor (CORTR) were examined by enzyme-linked immunosorbent assay.

Comparing the same group between different seasons, we showed that in the normal control group, CRH, ACTH, corticosterone, and MTR were higher, while CORTR was lower in autumn and winter than in spring (all P < .05). Compared with the normal control group, the pinealectomized group showed higher levels of corticosterone (P = .01), MTR (P = .01), and CORTR (P = .03) during spring; reduced levels of MTR and CORTR (both P < .001) during summer; higher levels of ACTH (P = .001) and MTR (P < .001), and lower levels of CRH (P = .001), corticosterone (P < .001), and CORTR (P = .003) during autumn; and lower levels of CRH (P < .001) and MTR (P = .004), and higher level of ACTH (P < .001) in winter.

Seasonal photoperiod acts on the pineal gland to secrete different levels of melatonin, resulting in seasonal changes in the hypothalamic-pituitary-adrenal axis-hippocampal-receptor, which may be the pathophysiological basis for the onset of seasonal affective disorder.

Based on the theory of "five Zang-organs corresponding to the seasons" in traditional Chinese medicine (TCM), physiological functions including emotions vary with the seasons. We aimed to investigate the seasonal photoperiod effects of melatonin (MT) released from the pineal gland on the MT receptor (MTR)-Gs/Gi-cyclic adenosine monophosphate (cAMP)-protein kinase A (PKA)-cAMP response element-binding protein (CREB) signaling pathway in the hippocampus.

Rats were divided into three groups: control, operation (surgery with pineal gland removal), and pseudo-operation groups (same surgery as operation group but without removing pineal gland), and fed at specific time across the four seasons. The levels of MTR, adenylate cyclase (AC), cAMP, PKA, and CREB in the hippocampus were analyzed using ELISA. The concentrations of Gs and Gi were analyzed using Western blot. The expression of CREB mRNA was detected by PCR.

For intragroup comparisons, compared with spring, the levels of Gs/Gi in the control group were higher in summer, autumn, and winter (P = .009 in summer; P < .001 in autumn and winter); the levels of MTR, cAMP, PKA, and CREB in the control group were significantly higher in autumn and winter than in spring (all P < .001). The levels of MTR, cAMP, PKA, and CREB in each season were significantly lower in the operation group than in the control group (all P < .05). Significant differences were noted in Gs/Gi levels between the operation group and control group in spring, autumn, and winter (all P < .05).

Our findings suggest that MTR-Gs/Gi-cAMP-PKA-CREB signaling pathway is involved in the seasonal photoperiod effects of the pineal gland on the hippocampus and may underpin seasonal changes in emotions. It can support the prevention and treatment of the seasonal onset of mental disorders, and enrich the theory of "five Zang-organs corresponding to the seasons".

In this study, we examined the effects of Shizhenqing granule (SZQG) on hypothalamic-pituitary-adrenal (HPA) axis and serum inflammatory factors in a rat model of chronic eczema, in order to explore the mechanism of action of SZQG in treatment of this disease.

Sixty Sprague–Dawley male rats were randomly divided into six groups (with 10 rats per group): blank group; model group; positive control group (prednisone); and the low-, medium-, and high-dose SZQG groups. Except for the blank group, rats in all other groups were treated with 2,4-dinitrochlorobenzene to induce chronic eczema. These rats were administered prednisone or SZQG for 7 consecutive days after successful establishment of the chronic eczema model, and samples were collected 12 h after the last administration. The degree of skin lesions and the changes in serum levels of corticotropin-releasing hormone (CRH), adrenocorticotropic hormone (ACTH), cortisol (CORT), interleukin (IL)-4, interferon (IFN)-γ, IL-25, and IL-31 among the groups were compared.

SZQG effectively increased the levels of CRH, ACTH, and CORT, which decreased in the serum of rats with chronic eczema, stimulated the function of the HPA axis, and promoted the expression of glucocorticoids. SZQG reduced the serum levels of inflammatory factors including IL-4, IL-25 and IL-31, which were overexpressed in rats with chronic eczema, and increased those of anti-inflammatory factor IFN-γ, thereby alleviating the inflammatory symptoms and itching, and ameliorating the clinical symptoms of chronic eczema.

SZQG effectively alleviates skin lesions in the chronic eczema rat model by stimulating the function of the HPA axis.

The present study aimed to investigate the effect of seasonal variation on neurotransmitter release in the hippocampus of normal rats and rats with pineal excision.

Two time points, the summer and winter solstice, which are the longest and shortest days of the year, respectively, were selected. Male Sprague–Dawley rats that underwent a sham operation without pineal excision were included as a control group. The concentrations of 5-hydroxytryptamine (5-HT) and γ-aminobutyric acid (GABA) were determined by radioimmunoassays and enzyme-linked immunosorbent assays, respectively.

In the winter, the 5-HT and GABA levels in normal rats exhibited a significant difference compared with those in the operation group (P < .01). A difference was also noted in GABA levels between the normal group and the sham operation group (P < .05). The concentrations of 5-HT and GABA in the hippocampal tissues of the normal group exhibited a seasonal rhythm consisting of elevation during the summer and reduction during the winter (P < .01), while the GABA levels in the sham operation group exhibited a significant difference, with elevation during the summer and reduction during the winter (P < .01). In the operation group, GABA showed the same trend (P < .01).

The seasonal rhythm of neurotransmitter secretion by the hippocampus (5-HT and GABA) consisted of elevation during the summer and reduction during the winter. During the winter, the pineal gland exhibited a reverse regulatory effect on the secretion of 5-HT and GABA in the hippocampus, and it exhibited seasonal selectivity with regard to the regulation of 5-HT.