Stable immune function during moult regardless of age‐specific moulting strategy in a European passerine

Energetic demands are high while energy availability is minimum during winter. To cope with this energetic bottleneck, animals exhibit numerous energy-conserving adaptations during winter, including changes in immune and reproductive functions. A majority of individual rodents within a population inhibits reproductive function (responders) as winter approaches. A substantial proportion of small rodents within a species, however, fails to inhibit reproduction (nonresponders) during winter in the field or in the laboratory when maintained in winter-simulated day lengths. In contrast, immune function is bolstered by short day lengths in some species. The specific mechanisms that link reproductive and immune functions remain unspecified. Leptin is a hormone produced by adipose tissue, and several studies suggest that leptin modulates reproductive and immune functions. The present study sought to determine if photoperiodic alterations in reproductive function and leptin concentrations are linked to photoperiod-modulated changes in immune function. Siberian hamsters (Phodopus sungorus) were housed in either long (LD 16:8) or short (LD 8:16) day lengths for 9 wk. After 9 wk, blood samples were collected during the middle of the light and dark phase to assess leptin concentrations. One week later, animals were injected with keyhole limpet hemocyanin to evaluate humoral immunity. Body mass, body fat content, and serum leptin concentrations were correlated with reproductive responsiveness to photoperiod; short-day animals with regressed gonads exhibited a reduction in these measures, whereas short-day nonresponders resembled long-day animals. In contrast, immune function was influenced by photoperiod but not reproductive status. Taken together, these data suggest that humoral immune function in Siberian hamsters is independent of photoperiod-mediated changes in leptin concentrations.

BackgroundSupplementation of nutritional deficiencies helps to improve immune function and resistance to infections in malnourished subjects. However, the suggested benefits of dietary supplementation for immune function in healthy well nourished subjects is less clear. Among the food constituents frequently associated with beneficial effects on immune function are micronutrients such as vitamin C, vitamin E, β-carotene and zinc, and colostrum. This study was designed to investigate the effects these ingredients on immune function markers in healthy volunteers.MethodsIn a double-blind, randomized, parallel, 2*2, placebo-controlled intervention study one hundred thirty-eight healthy volunteers aged 40–80 y (average 57 ± 10 y) received one of the following treatments: (1) bovine colostrum concentrate 1.2 g/d (equivalent to ~500 mg/d immunoglobulins), (2) micronutrient mix of 288 mg vitamin E, 375 mg vitamin C, 12 mg β-carotene and 15 mg zinc/day, (3) combination of colostrum and micronutrient mix, or (4) placebo. Several immune function parameters were assessed after 6 and 10 weeks. Data were analyzed by analysis of variance. Groups were combined to test micronutrient treatment versus no micronutrient treatment, and colostrum treatment versus no colostrum treatment.ResultsOverall, consumption of the micronutrient mix significantly enhanced delayed-type hypersensitivity (DTH) responses (p < 0.05). Adjusted covariance analysis showed a positive association between DTH and age. Separate analysis of younger and older age groups indicated that it was the older population that benefited from micronutrient consumption. The other immune function parameters including responses to systemic tetanus and oral typhoid vaccination, phagocytosis, oxidative burst, lymphocyte proliferation and lymphocyte subset distribution were neither affected by the consumption of micronutrients nor by the consumption of bovine colostrum concentrate.ConclusionConsumption of bovine colostrum had no effect on any of the immune parameters assessed. The micronutrient mix enhanced cellular immunity as measured by DTH, with an increased effect by incremental age, but did not affect any of the other immune parameters measured. Although correlations between decreased DTH and enhanced risk of certain infection have been reported, it remains unclear whether and enhanced DTH response actually improves immune defense. The present data suggests that improvement of immune parameters in a population with a generally good immune and nutritional status is limited and that improvement of immune function in this population may be difficult.

a competent immune system is crucial for maintaining a sufficiently high level of disease resistance. Immunity, however, is a double-edged sword. Impaired immunity increases susceptibility to pathogens and can increase the likelihood of sickness or death. Excessively heightened immune responses, in

Objective To observe the dynamic changes of the immune function in patients with esophageal cancer during the radiotherapy and also to explore its association with the clinical prognosis factors. Methods Totally 90 cases with esophageal cancer received radiotherapy in Second Affiliated Hospital of Nantong University from January 2010 to December 2013 were collected. The proportions of T-lymphocyte subsets and natural killer (NK) cells in the peripheral blood were detected by the flow cytometry from start to finish and 3 months after radiotherapy. Meanwhile, 30 cases of healthy subjects were taken as control. The changes of the immune function in the patients during the radiotherapy and the correlation between the changes and clinicopathologic features were analyzed, as well as the clinical prognostic factors were further evaluated. Results The difference of proportions of CD4+ T cells (28.23%±8.22%), CD8+ T cells (31.79%±7.61%), CD4+ /CD8+ ratio (0.93±0.34) and NK cells (11.37%±4.57%) in pre-radiotherapy patients with esophageal cancer were statistically significant (t=4.292, P=0.000; t=2.811, P=0.006; t=5.894, P=0.000; t=3.965, P=0.000) compared with control group (36.03%±9.71%, 27.26%±7.70%, 1.34±0.27, 15.31%±5.13%); but the proportions of CD3+ T cells (58.13%±9.46%) had no obvious difference (t=0.988, P=0.325) compared with control group (60.06%±8.67%). The immune function of esophageal patients in 3 months after radiotherapy such as CD3+ (59.27%±9.92%), CD4+ (30.51%±9.04%), CD8+ (29.79%±6.98%) and NK cells (10.62%±4.43%) gradually returned to the pre-radiotherapy levels (t=0.789, P=0.431; t=1.769, P=0.079; t=1.837, P=0.068; t=1.113, P=0.267). The changes of immune function (CD4+ , CD8+ , CD4+ /CD8+ ratio, NK cells) after radiotherapy were related to the bone marrow suppression (t=4.050, P=0.001; t=2.180, P=0.015; t=2.130, P=0.020; t=3.520, P=0.003) and irradiation volumes (t=5.170, P=0.000; t=3.350, P=0.026; t=8.750, P=0.000; t=2.490, P=0.043). Survival analysis showed that the patients whose immune function recovered better in 3 months after radiotherapy had a longer median survival time than those recovered bad (23 months vs. 17 months, χ2=6.820, P=0.009). Conclusion The patients of esophageal cancer are immunosuppressive before radiotherapy and will further aggravated after radiotherapy. The degree of immunosuppression is associa-ted with bone marrow suppression and irradiation volumes. The immune function of patients are recovered in 3 months after radiotherapy, and the patients whose immune function recovered better have good prognosis. Key words: Esophageal neoplasms; Radiotherapy; T-lymphocyte subsets; Natural killer cells

Seasonal changes in day length enhance or suppress components of immune function in individuals of several mammalian species. Siberian hamsters (Phodopus sungorus) exhibit multiple changes in neuroendocrine, reproductive, and immune function after exposure to short days. The manner in which these changes are integrated into the host response to pathogens is not well understood. The present experiments tested the hypothesis that short-day changes in immune function alter the pathogenesis of septic shock and survival after challenge with endotoxin. Male and female Siberian hamsters raised in long-day photoperiods were transferred as adults to short days or remained in their natal photoperiod. Six to 8 weeks later, hamsters were injected i.p. with 0, 1, 2.5, 10, 25, or 50 mg/kg bacterial lipopolysaccharide (LPS) (the biologically active constituent of endotoxin), and survival was monitored for 96 h. Short days significantly improved survival of male hamsters treated with 10 or 25 mg/kg LPS and improved survival in females treated with 50 mg/kg LPS. Transfer from long to short days shifted the LD50 in males by approximately 90%, from 5.3 to 9.9 mg/kg, and in females from 11.1 to 15.0 mg/kg (+35%). Long-day females were more resistant than were males to lethal endotoxemia. In vitro production of the proinflammatory cytokine TNFalpha in response to LPS stimulation was significantly lower in macrophages extracted from short-day relative to long-day hamsters, as were circulating concentrations of TNFalpha in vivo after i.p. administration of LPS, suggesting that diminished cytokine responses to LPS in short days may mitigate the lethality of endotoxemia. Adaptation to short days induces changes in immune parameters that affect survival in the face of immune challenges.

The effects of reproductive condition and exogenous melatonin on immune function were investigated in castrated European starlings, Sturnus vulgaris. Photorefractory and photostimulated starlings exposed to long days were implanted with melatonin or with blank capsules. Photostimulated starlings with blank capsules exhibited reduced splenocyte proliferation in response to the T-cell mitogen, concanavalin A, compared with the other long-day birds. Exogenous melatonin prevented the suppression of immune function by photostimulation. Photorefractory starlings, with or without melatonin implants, exhibited enhanced immune function compared with photostimulated starlings implanted with blanks. This enhancement was not mediated by endogenous melatonin, but appeared to be related to changes in reproductive state. In addition to the traditional costs of reproduction in birds (e.g. raising of young), there may be a cost of the reproductive state of starlings (i.e. whether they are photorefractory or photostimulated). These data are, we believe, the first to indicate a direct effect of reproductive state on immune function that is independent of both photoperiod (i.e., changes in the duration of melatonin secretion) and gonadal steroids.

SYNOPSIS. Winter is energetically-demanding; thermoregulatory demands increase when food availability usually decreases. Physiological and behavioral adaptations, including termination of breeding, have evolved among nontropical animals to cope with winter energy shortages. Presumably, selection for mechanisms that permit physiological and behavioral anticipation of seasonal ambient changes have led to current seasonal breeding patterns for many populations. Energetically—challenging winter conditions can directly induce death via hypothermia, starvation, or shock; surviving these demanding conditions likely evokes significant stress responses. The stress of coping with energetically-demanding conditions may increase adrenocortical steroid levels to the extent that immune function is compromised. Individuals would enjoy a survival advantage if seasonally-recurring stressors could be anticipated and countered by shunting energy reserves to bolster immune function. The primary environmental cue that permits physiological anticipation of season is daily photoperiod, a cue that is mediated by melatonin. However, other environmental factors, such as low food availability and ambient temperatures, may interact with photoperiod to affect immune function and disease processes. Laboratory studies of seasonal changes in mammalian immune function consistently report that immune function is enhanced in short day lengths. Prolonged melatonin treatment mimics short days, and also enhances immune function in rodents. In sum, melatonin may be part of an integrative system to coordinate reproductive, immunologic, and other physiological processes to cope successfully with energetic stressors during winter. Social factors influence immune function and changes in social interactions may also contribute to seasonal changes in immune function. The mechanisms by which social factors are transduced into immune responses are largely unspecified. In order to understand the optimization of immune function it is necessary to understand the interaction of factors, on both mechanistic and functional levels, that affect immunity.

Gastric cancer, one of the most common cancers of the digestive tract, has high incidence and mortality rates. Until recently, surgery has been the most effective method of treatment for gastric cancer. Surgery, however, inevitably results in dysfunction of the autonomic nervous system, entry of tumor cells into the bloodstream, and immunosuppression during the perioperative period, all of which increase the risk of complications in patients with gastric cancer. Opioid receptors play an important role in the proliferation and secretion of cytotoxic factors by immune cells. Opiate usage inhibits immune cell function, reduces the release of cytotoxic factors, and enables tumor cells to evade the immune system, thereby increasing the risk of perioperative complications. Opioid antagonists may reverse opioid-mediated immunosuppression in several ways. However, studies on the molecular biology of opioid receptor antagonists in relation to their ability to improve immune function in patients with gastric cancer are limited. We first analyzed the cancer genome atlas stomach adenocarcinoma (TCGA-STAD) dataset to determine the correlation between changes in immune function and toll-like receptor 4 (TLR4) expression in patients with gastric cancer. A transwell co-culture system was established using CD8+T and mouse forestomach carcinoma (MFC) cells. CD8+T cells were treated with different concentrations of naloxone to determine the most effective concentration for killing the tumor cells. We then performed western blotting and quantitative realtime polymerase chain reaction to determine the expression of lymphocyte activation gene 3 (Lag3), perforin 1 (Prf1), programmed death ligand 1 (PD-1), T-cell immunoglobulin and mucin domain 3 (TIM-3), and TLR4/AKT/mTOR in CD8+ T cells. An MFC-derived allograft mouse model was used to study the in vivo changes in the immune cells. Flow cytometry, ELISA, WB, and PCR were used to examine changes in the number of immune cell populations in the spleen, secretion of cytotoxic factors by immune cells, opioid receptors, AKT/mTOR, and immune checkpoint proteins, respectively, in CD8+T cells. We found that changes in perioperative immune function strongly correlated with TLR4 expression on the surface of immune cells in patients with gastric cancer. Low-dose naloxone (LDN) increased CD8+ T cell cytotoxicity, inhibited CD8+ T cell exhaustion, inhibited Lag3, Prf1, and Tim3 expression, and increased AKT and mTOR expression in CD8+ T cells. Opioid receptors were downregulated in CD8+ T cells following LDN administration. LDN improved the ability of CD8+T cells to kill gastric cancer cells and reduced CD8+T cell exhaustion. The mechanism underlying these LDN-mediated phenomena may involve regulation of immune checkpoint expression in CD8+ T cells, increased cytotoxic factor secretion by CD8+ T cells via the TLR4/AKT/mTOR pathway, or regulation of expression of opioid receptors on CD8+T cells, thereby further affecting CD8+T cell exhaustion.

122. An investigation into the impact of pregnancy and stress on neuroimmune function and whether there is a link to postpartum depression

Immune function in cigarette smokers who quit smoking for 31 days

Time-Dependent Differential Changes of Immune Function in Rats Exposed to Chronic Intermittent Noise

Effects of exam stress on mood, cortisol, and immune functioning: Influences of neuroticism and smoker-non-smoker status

During exercise, body temperature rises as a result of increased energy metabolism and heat absorbed from the environment. In response to this rise in body temperature, blood flow increases and stress hormones are released. Together, blood flow and stress hormones stimulate increases in the number of circulating leukocytes and alterations in various aspects of immune function, including cytokine production. The extent of changes in leukocyte numbers, cytokine concentrations, and immune cell function depends on how high body temperature rises and the intensity and duration of exercise. In general, increases in body temperature of ≤ 1.8° F (1° C) induce mild changes in immune function, and such changes are unlikely to increase the risk of illness in athletes, firefighters, and military personnel who regularly exercise in hot conditions. More severe immune disturbances during exercise in extreme heat (≥ 106° F or 41° C) may contribute to classical symptoms of heatstroke.

Endurance exercise can cause immunosuppression and increase the risk of upper respiratory illness. The present study examined changes in the secretion of T helper (Th) cell cytokines after endurance exercise. Ten highly trained road cyclists [mean±SEM: age 24.2±1.7 years; height 1.82±0.02 m; body mass 73.8±2.0 kg; peak oxygen uptake 65.9±2.3 mL/(kg•min)] performed 2 h of cycling exercise at 90% of the second ventilatory threshold. Peripheral blood mononuclear cells were isolated and stimulated with phytohemagglutinin. Plasma cortisol concentrations and the concentration of Th1/Th2/Th17 cell cytokines were examined. Data were analyzed using both traditional statistics and magnitude-based inferences. Results revealed a significant decrease in plasma cortisol at 4-24 h postexercise compared with pre-exercise values. Qualitative analysis revealed postexercise changes in concentrations of plasma cortisol, IL-2, TNF, IL-4, IL-6, IL-10, and IL-17A compared with pre-exercise values. A Th1/Th2 shift was evident immediately postexercise. Furthermore, for multiple cytokines, including IL-2 and TNF (Th1), IL-6 and IL-10 (Th2), and IL-17 (Th17), no meaningful change in concentration occurred until more than 4 h postexercise, highlighting the duration of exercise-induced changes in immune function. These results demonstrate the importance of considering "clinically" significant versus statistically significant changes in immune cell function after exercise.

: We have examined the immunotoxicological effects of JP-8 jet fuel exposure. Inbred C57BL6 mice were exposed to varying concentration (100-250 mg/m3) of aerosolized JP-8 jet fuel varying periods of time, using a variety of experimental models. Animal exposure was performed via nose-only presentation while the animals were held in individual subject loading tubes. The tubes were nose cone fitted to receiving adapters that originated from a common anodized aluminum exposure chamber. Nose only exposure was utilized to minimize ingestion of jet fuel during self-grooming, and to simulate human occupational exposures. Animals were rotated on a daily basis through the 12 adapter positions on the exposure chamber. This rotation was done to minimize proximity to the jet fuel source as a variable in exposure concentration or composition. Exposure concentration was determined by a seven-stage cascade impactor, and was measured after each exposure (1,2). At various times after the jet fuel exposures the animals were sacrificed and examined for changes in immune system composition and function. The major immune system organ systems (i.e., spleen, thymus, lymph nodes, blood and bone marrow) were recovered and examined for changes in organ weight, total cell numbers, immune cell components (by differential histochemical staining), and lymphocyte subpopulations by flow cytometric analyses. Assays were also performed to assess any changes in immune function in these organs. In some experiments the animals were administered an aerosolized concentration of the neuropeptide substance P (SP) in an effort to protect from or reverse the effects of JP-8 exposure.