Effect of Natural Seasonal Changes in Photoperiod and Temperature on Immune Function in Striped Hamsters.

What environmental factors contribute to seasonal variation in immune function in striped hamsters (Cricetulus barabensis) remains unclear. How immune responses would respond to natural seasonal changes in photoperiod and temperature was investigated in the present study. Twenty-nine male and 30 female hamsters were randomly assigned to the winter, spring, summer, and autumn groups. Spleen mass was the highest in male hamsters during autumn, while it did not differ among seasons in females. Regardless of sex, bacteria killing activity (BKA) was the lowest in the spring, whereas phytohaemagglutinin (PHA) responses at 12 h, 24 h, and 48 h were all highest in the winter among the four seasons. Females had the lowest titers of immunoglobin (Ig)G5, 10, and 15 in winter, while they did not show seasonal variation in males. Compared with male hamsters, females had higher levels of IgG10 and IgG15 in the spring and autumn, but had lower BKA in autumn. Blood glucose was the lowest in the spring in both sexes. Males had higher leptin level in winter than in summer and autumn, while leptin level was higher in winter and spring than in autumn in females. Corticosterone level was higher in winter and summer than in spring and autumn in males, while it was higher in winter than in the other three seasons in females. Males had higher levels of leptin in winter, and corticosterone in summer, than females. In summary, distinct parts of the immune system respond differently to natural seasonal variations in photoperiod and temperature.

Leptin mediates the suppressive effect of partial fat removal on cellular and humoral immunity in striped hamsters.

Leptin secreted mainly by white adipose tissues (WAT) plays an important role in immune responses. To understand the role of energy status and leptin in immunity, bilateral perigonadal fat pads were removed or sham-removed in male striped hamsters (Cricetulus barabensis). Half of these hamsters were injected with sterile saline, and another half were administrated with exogenous leptin each day, which lasted for 20 days. Fat removal reduced total body fat mass and leptin titers significantly, leptin administration increased leptin levels in the fat removed hamsters to the control levels, but did not affect total body fat mass. Body mass and gross energy intake were not affected by fat removal, leptin supplement or their interaction. Fat removal decreased thymus mass, phytohaemagglutinin (PHA) response at 12 h, and the levels of immunoglobin (Ig) G 5, IgG10, IgM5, IgM10, IL-2, IL-4, and TNF-α, indicating a reduction in fat mass suppressed cellular and humoral immunity and the production of cytokines. However, fat removal had no effect on spleen mass, bacteria killing activity and IFN-γ titers. Leptin supplement increased PHA response at 6 h and 12 h, and the levels of IgG5, IgG10, IL-4, and IFN-γ to the control levels, implying its boosting effects on these parameters. In addition, leptin level was positively correlated with body fat mass, PHA 6 h, 12 h, Ig G10, Ig M5, Ig M10, IL-2, IL-4, and TNF-α. Collectively, these findings implied leptin was a link between energy status and immunity, and leptin mediated the suppressive effects of reduced energy storage on cellular and humoral immunity.

Effects of air temperatures on antioxidant defense and immunity in Mongolian gerbils.

Temperature influences many physiological processes including antioxidant defense and immunity. The hypothesis that air temperatures has no effects on antioxidant defense and innate immunity in Mongolian gerbils (Meriones unguiculatus) was tested. Thirty-three male gerbils were randomly divided into the 4 °C (n = 11), 23 °C (n = 11) and 32 °C groups (n = 11), in which the treatment course lasted for 27 days. We found that air temperatures had no effects on body mass. At lower temperature, gross energy intake and the masses of most organs were higher, whereas fat free dry carcass and body fat were lower. H2O2 titres increased in liver but decreased in small intestine, and remained unchanged in heart, kidney and testis upon cold exposure. At lower temperature, malonaldehyde (MDA) content was higher in the liver, lower in kidneys and testis, and did not differ in the heart and small intestine. The activities of superoxide dismutase (SOD), total antioxidant capacity (T-AOC) in liver were higher in 4 °C group than 23 °C group, while liver catalase (CAT) activity was lower in the 4 °C group than in the 23 °C group. No significant difference was observed in the activities of SOD, CAT and T-AOC in the heart, kidney, testis and small intestine among the 4 °C, 23 °C and 32 °C groups. As expected, bacteria killing capacity indicating innate immunity, white blood cells and thymus mass were all not affected by air temperatures. Similarly, air temperatures had no effect on the levels of testosterone and corticosterone, both of which were not correlated with innate immunity, H2O2 and MDA levels, the activity of SOD, CAT, and T-AOC in all the detected tissues. In conclusion, air temperature affected antioxidant capacity, but not immune responses or serum concentrations of corticosterone and testosterone. Overall, up-regulation or maintenance of antioxidant defenses and immunity might be an important mechanism for gerbils to survive highly variable temperature.

Effect of temperature and food restriction on immune function in striped hamsters (Cricetulus barabensis).

Small mammals in temperate areas face seasonal fluctuations of temperature and food availability, both of which may influence their immune responses, which are critical to survival. In the present study, we tested the hypothesis that low temperature and food restriction suppress immune function in striped hamsters (Cricetulus barabensis). Thirty-seven adult male hamsters were randomly assigned to warm (23±1°C) and cold (5±1°C) treatment groups, which were further divided into fed and food-restricted groups. Body mass was not affected by cold stress, food restriction or the interaction cold stress×food restriction. Cold stress decreased total body fat mass, haematological parameters including white blood cells, lymphocytes and neutrophilic granulocytes, and immunoglobin (Ig) M titres 5 days after injecting keyhole limpet haemocyanin (KLH). However, cold temperature increased bacterial killing capacity, indicative of innate immunity, and did not affect the mass of the thymus and spleen, intermediate granulocytes, the phytohaemagglutinin (PHA) response and the levels of blood glucose and serum leptin. Corticosterone concentration was affected significantly by the interaction cold stress×food restriction but not by cold stress or food restriction alone. Food restriction reduced thymus mass, but other immunological parameters including body fat mass, spleen mass, haematological parameters, innate immunity, PHA response, the titres of IgM and IgG, and the levels of blood glucose and serum leptin were all not affected by food restriction or the interaction cold stress×food restriction. Innate immunity was positively correlated with leptin levels, whereas no significant correlations were observed in the levels of blood glucose, serum leptin, corticosterone and all the detected immune parameters. Our results show that cold stress suppressed humoral immunity but enhanced innate immunity and did not affect cellular immunity in striped hamsters. Most immunological indices were not influenced by food restriction. Blood glucose, leptin and corticosterone could not explain the changes of innate, cellular and humoral immunity upon cold stress or food restriction in striped hamsters.

Photoperiod and temperature differently affect immune function in striped hamsters (Cricetulus barabensis).

Small mammals generally use short day length to elevate immune function to counteract the immunosuppressive effect of low temperature in winter in light of the winter immunoenhancement hypothesis. In the present study, we tested this hypothesis in striped hamsters (Cricetulus barabensis). We expected that immune responses would be increased by short photoperiod but suppressed by low temperature. Thirty-four adult female hamsters were randomly divided into the long day (16L:8D) and short day (8L:16D) groups, which were further assigned into the warm (23±1°C) and the cold (5±1°C) groups, respectively. We found that body mass was not affected by photoperiod or temperature. Contrary to our expectation, short day reduced phytohaemagglutinin (PHA) response indicative of cellular immunity and the levels of immunoglobin (Ig) M. It had no effect on total body fat mass, thymus and spleen masses, white blood cells (WBC) and Ig G titers. As expected, cold stress decreased total body fat mass, WBC, Ig G and Ig M titers. However, it did not influence the masses of thymus and spleen and PHA responses. The levels of blood glucose, serum leptin and corticosterone were all not affected by temperature or photoperiod except that corticosterone levels were increased by short days. No significant correlations were detected among the levels of blood glucose, serum leptin, corticosterone and all the detected immunological parameters. Taken together, short photoperiod suppressed both cellular and humoral immunity in striped hamsters, which did not support the winter immunoenhancement hypothesis. Cold stress reduced humoral immunity and WBC, which might account for the highest mortality in winter in this species. Blood glucose, leptin and corticosterone could not interpret the changes of immunity in hamsters.

Accelerating precision anti-cancer therapy by time-lapse and label-free 3D tumor slice culture platform.

The feasibility of personalized medicine for cancer treatment is largely hampered by costly, labor-intensive and time-consuming models for drug discovery. Herein, establishing new pre-clinical models to tackle these issues for personalized medicine is urgently demanded. Methods: We established a three-dimensional tumor slice culture (3D-TSC) platform incorporating label-free techniques for time-course experiments to predict anti-cancer drug efficacy and validated the 3D-TSC model by multiphoton fluorescence microscopy, RNA sequence analysis, histochemical and histological analysis. Results: Using time-lapse imaging of the apoptotic reporter sensor C3 (C3), we performed cell-based high-throughput drug screening and shortlisted high-efficacy drugs to screen murine and human 3D-TSCs, which validate effective candidates within 7 days of surgery. Histological and RNA sequence analyses demonstrated that 3D-TSCs accurately preserved immune components of the original tumor, which enables the successful achievement of immune checkpoint blockade assays with antibodies against PD-1 and/or PD-L1. Label-free multiphoton fluorescence imaging revealed that 3D-TSCs exhibit lipofuscin autofluorescence features in the time-course monitoring of drug response and efficacy. Conclusion: This technology accelerates precision anti-cancer therapy by providing a cheap, fast, and easy platform for anti-cancer drug discovery.

Fasting suppresses T cell-mediated immunity in female Mongolian gerbils (Meriones unguiculatus).

Immune defense is important for organisms' survival and fitness. Small mammals in temperate zone often face seasonal food shortages. Generally fasting can suppress immune function in laboratory rodents and little information is available for wild rodents. The present study tested the hypothesis that Mongolian gerbils (Meriones unguiculatus) could inhibit T cell-mediated immunity to adapt to acute fasting. Forty-two females were divided into the fed and fasted groups, in which the latter was deprived of food for 3days. After 66h fasting, half of the gerbils in each group were injected with phosphate buffered saline or phytohaemagglutinin (PHA) solution. T cell-mediated immunity assessed by PHA response was suppressed in the fasted gerbils compared with the fed gerbils. The fasted gerbils had lower body fat mass, wet and dry thymus mass, dry spleen mass, white blood cells, serum leptin and blood glucose concentrations, but higher corticosterone concentrations than those of the controls. Moreover, PHA response was positively correlated with body fat mass and serum leptin levels in the immunochallenged groups. Taken together, acute fasting leads to immunosuppression, which might be caused by low body fat mass and low serum leptin concentrations in female Mongolian gerbils.

Season and sex have different effects on hematology and cytokines in striped hamsters (Cricetulus barabensis).

Animals in the temperate zones face seasonal variations in environments and hence their immune responses change seasonally. In the current study, seasonal changes in hematological parameters and cytokines in striped hamsters (Cricetulus barabensis) were examined to test the winter immunoenhancement hypothesis, which states that immune function tends to increase in fall and winter compared with other seasons. Male and female hamsters were captured from the wild in the fall and winter of 2014 and in the spring and summer of 2015. Maximum body mass in both sexes and relative fatness in female hamsters occurred in the summer, indicating that body condition was the best during this season. All hematological parameters were not different between male and female hamsters, and were also not affected by the interaction of season and sex except neutrophil granulocytes (GRAN). Red blood cells (RBC) and haematocrit (PCV) were higher in the fall and winter, and hemoglobin concentration (HGB) was the highest in winter in hamsters compared with the spring and summer, implying that their oxygen-carrying capacity and oxygen affinity of the blood increased during these seasons. Compared with other seasons, the number of white blood cells (WBC) was higher in winter than in summer, intermediate granulocytes (MID), the percent of MID (MID%), GRAN and the percent of GRAN (GRAN%) were the highest in winter, which all supported the winter immunoenhancement hypothesis. However, the count of lymphocytes (LYMF) was the highest in spring, being inconsistent with this hypothesis. IL-2 levels, but not TNF-α, were influenced by seasons, sex and their interaction in hamsters. Regardless of sex, IL-4 titres were higher in spring and summer than in fall and winter in hamsters. INF-γ titres in male hamsters did not differ between the spring and summer, while its titres in female hamsters was lower in spring in contrast with winter and summer. Higher IL-2 and IL-4 levels during the breeding seasons might be crucial in controlling the increased possibilities of infections in these seasons. In summary, season and sex had disparate effects on different hematological profiles and the levels of cytokines in hamsters.

Effect of temperature on antioxidant defense and innate immunity in Brandt's voles.

Ambient temperature is an important factor influencing many physiological processes, including antioxidant defense and immunity. In the present study, we tested the hypothesis that antioxidant defense and immunity are suppressed by high and low temperature treatment in Brandt's voles (Lasiopodomys brandtii). Thirty male voles were randomly assigned into different temperature groups (4, 23, and 32 °C, n=10 for each group), with the treatment course lasting for 27 d. Results showed that low temperature increased gross energy intake (GEI) and liver, heart, and kidney mass, but decreased body fat mass and dry carcass mass. With the decline in temperature, hydrogen peroxide (H2O2) concentration, which is indicative of reactive oxygen species (ROS) levels, increased in the liver, decreased in the heart, and was unchanged in the kidney, testis, and small intestine. Lipid peroxidation indicated by malonaldehyde (MDA) content in the liver, heart, kidney, testis, and small intestine did not differ among groups, implying that high and low temperature did not cause oxidative damage. Similarly, superoxide dismutase (SOD) and catalase (CAT) activities and total antioxidant capacity (T-AOC) in the five tissues did not respond to low or high temperature, except for elevation of CAT activity in the testis upon cold exposure. Bacteria killing capacity, which is indicative of innate immunity, was nearly suppressed in the 4 °C group in contrast to the 23 °C group, whereas spleen mass and white blood cells were unaffected by temperature treatment. The levels of testosterone, but not corticosterone, were influenced by temperature treatment, though neither were correlated with innate immunity, H2O2 and MDA levels, or SOD, CAT, and T-AOC activity in any detected tissues. Overall, these results showed that temperature had different influences on oxidative stress, antioxidant enzymes, and immunity, which depended on the tissues and parameters tested. Up-regulation or maintenance of antioxidant defense might be an important mechanism for voles to survive highly variable environmental temperatures.

Seasonal variations in cellular and humoral immunity in male striped hamsters (Cricetulus barabensis).

Animals in the non-tropical zone usually demonstrate seasonal variations in immune function, which is important for their survival. In the present study, seasonal changes in immunity in striped hamsters (Cricetulus barabensis) were investigated to test the winter immunoenhancement hypothesis. Male hamsters were captured from the wild in the fall and winter of 2014 and in the spring and summer of 2015. Body mass, body fat mass and blood glucose levels of the hamsters were all highest in the summer, whereas relative fatness and thymus mass had no seasonal changes. Spleen mass was highest in the fall and white blood cells and phytohaemagglutinin (PHA) response indicative of cellular immunity were lowest in the summer among the four seasons, which supports the winter immunoenhancement hypothesis. IgG and IgM titers were lowest in the fall, which was against this hypothesis. Body fat mass had no correlations with cellular and humoral immunity, suggesting it was not the reason for seasonal changes in cellular and humoral immunity in males. Leptin titers were higher in spring and summer than in fall and winter. No correlation between leptin and cellular and humoral immunity suggested that leptin did not mediate their seasonal changes. Similarly, corticosterone levels were also higher in spring and summer than in fall and winter, which correlated negatively with cellular immunity but positively with IgG levels. This result implied that corticosterone has a suppressive effect on cellular immunity and an enhancing effect on humoral immunity. In summary, distinct components of immune systems exhibited different seasonal patterns. This article has an associated First Person interview with the first author of the paper.

Glucose supplement reverses the fasting-induced suppression of cellular immunity in Mongolian gerbils (Meriones unguiculatus).

Glucose plays an important role in immunity. Three day fasting will decrease cellular immunity and blood glucose levels in Mongolian gerbils (Meriones unguiculatus). In the present study, we tested the hypothesis that glucose supplement can reverse the fasting-induced suppression in cellular immunity in gerbils. Twenty-eight male gerbils were selected and randomly divided into fed and fasting groups. Half of the gerbils in each group were then provided with either 10% glucose water or pure water. After 66 h, each gerbil was injected with phytohaemagglutinin (PHA) solution to challenge cellular immunity. Results showed that glucose supplement restored blood glucose levels in fasted gerbils to those of the fed controls. It also recovered cellular immunity, body fat mass and serum leptin levels in fasted gerbils to the values of the fed controls. Blood glucose levels were positively correlated with body fat mass, leptin levels and cellular immune responses. Thymus and spleen masses, and white blood cells in fasted gerbils were not affected by glucose supplement. In general, our data demonstrate that glucose supplement could reverse fasting-induced suppression of cellular immunity in Mongolian gerbils.

Food restriction and refeeding have no effect on cellular and humoral immunity in Mongolian gerbils (Meriones unguiculatus).

Small mammals in the temperate area often face fluctuations in food availability. Changes in food availability may have a great influence on an animals' immunity, which is important to their survival. We tested the hypothesis that cellular and humoral immunity would be suppressed by food restriction and restored to control levels by refeeding in Mongolian gerbils Meriones unguiculatus. Forty adult male gerbils were randomly divided into food-restricted (80% of baseline food intake) and food ad lib. groups. Similarly, another 40 adult male gerbils were also randomly assigned to two groups: a group for which food was restricted for 36 d and then provided ad lib. and a group that was continuously fed ad lib. Half of the gerbils in each group were injected with phytohemagglutinin (PHA) and keyhole limpet hemocyanin solution to assess cellular and humoral immunity, respectively; the others were injected with sterile saline as control groups. Food-restricted gerbils had significantly lower body mass, body fat mass, dry thymus mass, wet and dry spleen mass, and serum leptin levels than those of the controls, whereas refeeding restored these parameters to the controls. Both food restriction and refeeding had no significant effect on PHA response indicative of cellular immunity, immunoglobulin G and immunoglobulin M concentrations, and white blood cells. We also found that food restriction decreased corticosterone levels in food-restricted gerbils, while refeeding increased corticosterone levels in refed gerbils compared with the controls. Our results suggest that cellular and humoral immunity were not affected by food restriction and refeeding in gerbils.

WITHDRAWN: Fasting suppresses T cell-mediated immunity in female Mongolian gerbils (Meriones unguiculatus).

The Publisher regrets that this article is an accidental duplication of an article that has already been published, doi: 10.1016/j.cbpa.2009.09.003. The duplicate article has therefore been withdrawn.