Immune Response In Aged Mice Research Articles

The Benjamin Button effect on stem cells: Reversing the clock on aging immunity.

Antibody-based therapy depletes myeloid-biased hematopoietic stem cells (my-HSCs) to rejuvenate the immune system and improve immune responses in aged mice.

Age-induced changes in anti-tumor immunity alter the tumor immune infiltrate and impact response to immuno-oncology treatments.

Immuno-oncology (IO) research relies heavily on murine syngeneic tumor models. However, whilst the average age for a cancer diagnosis is 60 years or older, for practical purposes the majority of preclinical studies are conducted in young mice, despite the fact that ageing has been shown to have a significant impact on the immune response. Using aged (60-72 weeks old) mice bearing CT26 tumors, we investigated the impact of ageing on tumor growth as well as the immune composition of the tumor and peripheral lymphoid organs. We found many differences in the immune cell composition of both the tumor and tumor-draining lymph node between aged and young mice, such as a reduction in the naïve T cell population and a decreased intratumoral CD8/Treg ratio in aged animals. We hypothesized that these differences may contribute to impaired anti-cancer immune responses in aged mice and therefore assessed the anti-tumor efficacy of different IO therapies in aged mice, including both co-stimulation (using an anti-OX40 antibody) and immune checkpoint blockade (using anti-PD-L1 and anti-CTLA-4 antibodies). Whilst aged mice retained the capacity to generate anti-tumor immune responses, these were significantly attenuated when compared to the responses observed in young mice. These differences highlight the importance of age-related immunological changes in assessing and refining the translational insights gained from preclinical mouse models.

Improvement of the aging-related reduced efficacy of the H1N1 pandemic influenza vaccine by the complex of poly-γ-glutamic acid and alum

Abstract Highly contagious respiratory diseases caused by viral infections, like influenza are a constantly emerging threat, particularly among the elderly. Vaccination is one of the most effective strategy for preventing influenza, but the aged-related reduced efficacy of the influenza vaccine remains an unresolved problem. Here, we demonstrate that the aging-related reduced efficacy of the influenza vaccine can be improved by the complex of poly-γ-glutamic acid (γ-PGA) and alum called PGA/Alum, a new adjuvant capable of inducing innate and adaptive immune responses in aged mice. PGA/Alum induced activation of dendritic cells isolated from spleen of aged mice, with increases of expression of co-stimulatory molecules and production of pro-inflammatory cytokines. Although aged mice were observed decrease of T and B cell population and weaken efficacy of pandemic H1N1 influenza vaccine than young mice, PGA/Alum recovered the vaccine efficacy in aged mice. Notably, the vaccine-PGA/Alum-immunized aged mice increased hemagglutination-inhibition titers, serum-neutralization titers, cytotoxic T lymphocyte activity, and generation of multifunctional CD4+ T lymphocytes. Taken together, these results suggest that PGA/Alum could be a potent vaccine adjuvant that improves the aging-related reduced efficacy of the influenza vaccine, thereby resulting in effective prevention against influenza virus infection in the elderly. This research was funded by a grant from KRIBB Research Initiative Program (KGM9942112).

A booster dose enhances immunogenicity of the COVID-19 vaccine candidate ChAdOx1 nCoV-19 in aged mice

SummaryBackgroundThe spread of SARS-CoV-2 has caused a worldwide pandemic that has affected almost every aspect of human life. The development of an effective COVID-19 vaccine could limit the morbidity and mortality caused by infection and may enable the relaxation of social-distancing measures. Age is one of the most significant risk factors for poor health outcomes after SARS-CoV-2 infection; therefore, it is desirable that any new vaccine candidates elicit a robust immune response in older adults.MethodsHere, we use in-depth immunophenotyping to characterize the innate and adaptive immune response induced upon intramuscular administration of the adenoviral vectored ChAdOx1 nCoV-19 (AZD-1222) COVID-19 vaccine candidate in mice.FindingsA single vaccination generates spike-specific Th1 cells, Th1-like Foxp3+ regulatory T cells, polyfunctional spike-specific CD8+ T cells. and granzyme-B-producing CD8 effectors. Spike-specific IgG and IgM are generated from both the early extrafollicular antibody response and the T follicular helper cell-supported germinal center reaction, which is associated with the production of virus-neutralizing antibodies. A single dose of this vaccine generated a similar type of immune response in aged mice but of a reduced magnitude than in younger mice. We report that a second dose enhances the immune response to this vaccine in aged mice.ConclusionsThis study shows that ChAdOx1 nCoV-19 induces both cellular and humoral immunity in adult and aged mice and suggests a prime-boost strategy is a rational approach to enhance immunogenicity in older persons.FundingThis study was supported by BBSRC, Lister institute of Preventative Medicine, EPSRC VaxHub, and Innovate UK.

Silk Peptide Regulates the Level of Immunoglobulin from Young and Aged C57BL/6 Mice Serum

Immune system contributes to increasing old people chanced of developing metabolic disease in aged‐related change. Age‐associated changes of the immune system include the enhancement of a pre‐inflammatory cytokine and immunoglobulin production induces dysfunctional immune response. It is important to maintain proper amount of cytokine and immunoglobulin within the serum, but the elderly fail to maintain constancy in immune response. In particular, the immunoglobulin secreted by plasma B cells play a key role in the defense against pathogens in adaptive immunity. According to the homeostasis of immunoglobulin is very important. Aging increases levels of serum IgG, IgA and IgM, which reduces sensitivity to several antigen and causes a reaction to self‐antigen. We suggested regulate the homeostasis of immunoglobulin in aged mice serum by effective natural compound. Silk peptide is well known as bioactive component and a natural water‐soluble glycoprotein extracted from raw silk cocoons. However, remains unknown whether it is effective for immune response in aged mice. In this study, aged and young female C57BL/6 mice were orally administered the Silk peptide daily, and total serum were analyzed from aged and young mice. In conclusion, the increased amount of immunoglobulin in aged mouse serum was reduced as much as the young mouse by Silk peptide. This novel result determines that Silk peptide has potent to use in immune therapies to recover a humoral response of aging society.

Prime-pull vaccination with a plant-derived virus-like particle influenza vaccine elicits a broad immune response and protects aged mice from death and frailty after challenge

BackgroundAdministered intramuscularly (IM), plant-derived, virus-like-particle (VLP) vaccines based on the influenza hemagglutinin (HA) protein elicit both humoral and cellular responses that can protect aged mice from lethal challenge. Unlike split virus vaccines, VLPs can be administered by different routes including intranasally (IN). We evaluated novel vaccine strategies such as prime-pull (IM boosted by IN) and multi-modality vaccination (IM and IN given simultaneously). We wished to determine if these approaches would provide better quality protection in old mice after less severe (borderline-lethal) challenge (ie: immunogenicity, frailty and survival).ResultsSurvival rates were similar in all vaccinated groups. Antibody responses were modest in all groups but tended to be higher in VLP groups compared to inactivated influenza vaccine (IIV) recipients. All VLP groups had higher splenocyte T cell responses than the split virus group. Lung homogenate chemokine/cytokine levels and virus loads were lower in the VLP groups compared to IIV recipients 3 days after challenge (p < 0.05 for viral load vs all VLP groups combined). The VLP-vaccinated groups also had less weight loss and recovered more rapidly than the IIV recipients. There was limited evidence of an immunologic or survival advantage with IN delivery of the VLP vaccine.ConclusionCompared to IIV, the plant-derived VLP vaccine induced a broader immune response in aged mice (cellular and humoral) using either traditional (IM/IM) or novel schedules (multi-modality, prime-pull).

Abstract 4987: Age-induced changes in anti-tumor immunity alter the tumor immune infiltrate and reduce response to immuno-oncology treatments

Abstract Immuno-oncology research relies heavily on murine syngeneic tumor models. However, whilst the median age for a cancer diagnosis is 65 years or older, for practical purposes the majority of preclinical studies are conducted in young mice, despite the fact that aging has been shown to have a significant impact on the immune response. Using aged mice bearing CT26 tumors, we analysed how aging impacts the immune composition of the tumor, spleen and tumor-draining lymph nodes by flow cytometry. We found many age-related changes between aged (60-72 weeks old) and young (6-8 weeks old) mice, such as a reduction in the naïve T cell population and a decreased CD8/Treg ratio in aged animals. Profiling of co-inhibitory and co-stimulatory receptor expression levels on immune cells in aged versus young mice also identified altered expression profiles in both the periphery and tumor. We hypothesised that these differences may contribute to impaired anti-cancer immune responses in aged mice. To investigate this, we compared the anti-tumor efficacy of immune checkpoint blockade (PD-L1 and CTLA-4) and T-cell costimulation (OX-40) in aged versus young mice. Our data demonstrate that aged mice retained their capacity to generate effective anti-tumor immune responses, albeit often attenuated when compared to the responses observed in young mice. These differences highlight the potential importance of age-related immunological changes in assessing and refining the translational insights gained from preclinical mouse models. Citation Format: Suzanne I. Sitnikova, Michelle Morrow, Viia Valge-Archer, Robert W. Wilkinson, Simon J. Dovedi, Matthew J. Robinson. Age-induced changes in anti-tumor immunity alter the tumor immune infiltrate and reduce response to immuno-oncology treatments [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 4987.

Abstract TMP36: Sex Differences in Neutrophil-T Cell Immune Responses and Outcome After Ischemic Stroke in Aged Mice

Introduction: Sex differences in ischemic stroke are seen in clinical and experimental studies. Men have a higher risk of stroke throughout most of the life-span. Women have greater stroke mortality than men, however a recent multi-continental meta-analysis showed lower mortality in women when adjusted for age, pre-morbid function, stroke severity and other confounding factors. In experimental models, middle-aged female mice have larger strokes, likely due to the loss of estrogen. Less is known about outcomes in very aged animals. Hypothesis: Inflammatory responses are key determinants of stroke outcome and there are important sex differences in the immune response in aged mice. Methods: Male and female C57BL/6 mice (21-22 months) were subjected to 60 min middle cerebral artery occlusion (n=28-32), or sham surgery (n=16). Neutrophils and T cells were quantified in brain and blood at 24 h and 15 days post-stroke by flow cytometry. Functional outcomes were assessed at day 3, 7 and 14. Results: Male mortality was significantly higher than in females (41% vs 16%, P&lt;0.05). Hemorrhagic transformation was seen in 55% of the males that died (6/11) and in none of the females (0/4). Aged males had greater stroke-induced loss of body temperature, splenic contraction and gut permeability (FITC-dextran assay, n=6-7, P&lt;0.05). Acutely after stroke (24 h), aged males had significantly higher brain infiltration of neutrophils and plasma levels of MCP-1 and G-CSF compared to females. Aged males had elevated levels of CD8 + T cells in the blood compared to females at day 15 (73±5% of CD3 + T cells vs 52±3%, P&lt;0.001). Brain T regulatory cells were increased after stroke in males (P&lt;0.01), but not in females. Open-field test showed decreased center visits after stroke at day 3, however males spent more time immobile (P&lt;0.01), indicating decreased locomotor activity/anxiety. This difference equalized at 7 and 14 days post-stroke. Conclusion: Higher mortality and hemorrhagic transformation rates were seen in aged males compared to females after ischemic stroke. This was associated with higher levels of neutrophils/Tregs in the brain and CD8 + T cells in the blood suggesting a greater stroke-induced immune response in aged males.

Adipose Tissue Inflammation Induces B Cell Inflammation and Decreases B Cell Function in Aging.

Aging is the greatest risk factor for developing chronic diseases. Inflamm-aging, the age-related increase in low-grade chronic inflammation, may be a common link in age-related diseases. This review summarizes recent published data on potential cellular and molecular mechanisms of the age-related increase in inflammation, and how these contribute to decreased humoral immune responses in aged mice and humans. Briefly, we cover how aging and related inflammation decrease antibody responses in mice and humans, and how obesity contributes to the mechanisms for aging through increased inflammation. We also report data in the literature showing adipose tissue infiltration with immune cells and how these cells are recruited and contribute to local and systemic inflammation. We show that several types of immune cells infiltrate the adipose tissue and these include macrophages, neutrophils, NK cells, innate lymphoid cells, eosinophils, T cells, B1, and B2 cells. Our main focus is how the adipose tissue affects immune responses, in particular B cell responses and antibody production. The role of leptin in generating inflammation and decreased B cell responses is also discussed. We report data published by us and by other groups showing that the adipose tissue generates pro-inflammatory B cell subsets which induce pro-inflammatory T cells, promote insulin resistance, and secrete pathogenic autoimmune antibodies.

Innate Immune Response and Outcome of Clostridium difficile Infection Are Dependent on Fecal Bacterial Composition in the Aged Host

Clostridium difficile infection (CDI) is a serious threat for an aging population. Using an aged mouse model, we evaluated the effect of age and the roles of innate immunity and intestinal microbiota. Aged (18 months) and young (8 weeks) mice were infected with C difficile, and disease severity, immune response, and intestinal microbiome were compared. The same experiment was repeated with intestinal microbiota exchange between aged and young mice before infection. Higher mortality was observed in aged mice with weaker neutrophilic mobilization in blood and intestinal tissue and depressed proinflammatory cytokines in early infection. Microbiota exchange improved survival and early immune response in aged mice. Microbiome analysis revealed that aged mice have significant deficiencies in Bacteroidetes phylum and, specifically, Bacteroides, Alistipes, and rc4-4 genera, which were replenished by cage switching. Microbiota-dependent alteration in innate immune response early on during infection may explain poor outcome in aged host with CDI.

Live attenuated Leishmania donovani Centrin knock out parasites generate non-inferior protective immune response in aged mice against Visceral Leishmaniasis

Abstract Visceral Leishmaniasis (VL) causes significant mortality. Age appears to be critical in determining the clinical outcome of VL and there is no effective vaccine available against VL for any age group. Previously, we showed that gene deleted live attenuated L. donovani parasites (LdCen−/−) induced a strong protective immune response in young mice. In this study we analyzed LdCen−/− mediated modulation of immune response in aged mice (18 months) and compared to young (2 months) mice. Analysis of innate response in dendritic cells (DCs) from both young and aged mice upon infection with LdCen−/− parasites, showed significant enhancement of innate effector responses, which consequently augmented CD4+ Th1 cell effector function compared to LdWT infected DCs in vitro. Similarly, parasitized splenic DCs from LdCen−/− infected young and aged mice revealed induction of proinflammatory cytokines and down regulation of anti-inflammatory cytokine genes compared to LdWT infected mice. Furthermore, immunization with LdCen−/− induced higher IgG2a antibodies, lymphoproliferative response and stimulated splenocytes for heightened leishmanicidal activity in young and aged mice. Additionally, upon virulent L. donovani challenge, LdCen−/− immunized mice from both age groups displayed multifunctional Th1-type CD4 and cytotoxic CD8 T cells leading to significantly reduced parasite burden in the spleen and liver compared to naïve mice. Although, there was no difference in the LdCen−/− induced innate response in DCs between aged and young, the adaptive response in terms of T cell and B cell activation in aged was reduced, which correlated with LdCen−/− induced significant but diminished protective response in aged compared to young mice against VL.

Impairment of host resistance to helminthes with age in murine small intestine.

Age-associated alterations of Th2 immune responses against nematode parasites are largely unknown. We investigated primary and memory responses against two types of gastrointestinal nematode parasites, Heligmosomoides polygyrus (Hp) and Nippostrongylus brasiliensis (Nb), in aged mice. The small intestinal gene expression of Th2 cytokines was almost unchanged after primary (Nb and Hp) and secondary infection (Hp) in aged mice in contrast to strongly increased small intestinal gene expression of Th2 cytokines in young (3-month-old) mice. Mucus production decreased (Nb), and worm expulsion was impaired (Nb and Hp) compared with the young mice. Immunofluorescent staining revealed that after Hp infection, the number of alternatively activated macrophages, which are induced by Th2 cytokines, was lower in the aged mice. On the other hand, the number of CD4(+) T cells recruited to the worm cysts was normal compared with the young mice. These results suggest that migration of CD4(+) T cells to the host-parasite interface is not affected by ageing. Alterations in Th2 immune responses in aged mice might be due to inappropriate or insufficient activation of CD4(+) T cells in the submucosa.

Lentinula edodes-derived polysaccharide rejuvenates mice in terms of immune responses and gut microbiota.

Aging is characterized by impaired immunity and unbalanced gut microbiota. Prebiotics have the capability to prevent or reverse age-related declines in health by modulating gut microbiota. Mushroom polysaccharides have been suggested to be potential prebiotics. However, their effects on the immunity and gut microbiota in aged mice have not been determined. This study firstly assessed the effects of a heteropolysaccharide L2 isolated from the fruit body of L. edodes on the immune response of aged mice, and then compared the composition of fecal microbiota in adult (N), old (O) and L2-treated old (Oa) mice using the high-throughput pyrosequencing technique. The results showed that L2 can restore the age-attenuated immune responses by increasing cytokine levels in peripheral blood. Moreover, L2 can partly reverse the age-altered composition of gut microbiota. The Euclidean distances (De) among 3 groups (N, O and Oa) are determined to be De(O, N) = 0.19, De(O, Oa) = 0.20, and De(N, Oa) = 0.10, i.e. there is a marked reduction in the distance from 0.19 to 0.1 by L2. This suggests the beneficial effects of L2 on enhancing immunity and improving gut health.

Adipose-derived mesenchymal stem cells restore impaired mucosal immune responses in aged mice (P3162)

Abstract It has been shown that adipose-derived mesenchymal stem cells (AMSCs) can differentiate into red blood cells and epithelial cells as well as mesenchymal cells such as adipocytes, chondrocytes and osteoblasts. Various clinical trials have shown the ability of AMSCs to regenerate these cell types. Age-associated dysregulation of the gastrointestinal (GI) immune system has been well documented. Our previous studies showed that impaired mucosal immunity in the GI tract occurs earlier than is seen in the systemic compartment. In this study, we examined the potential of AMSCs to restore the GI mucosal immune system in aged mice. Aged (&amp;gt;2yr) mice were adoptively transferred with AMSCs. Two weeks later, mice were orally immunized with ovalbumin (OVA) plus cholera toxin three times at weekly intervals. Seven days after the final immunization, when fecal extract samples and plasma were subjected to OVA-specific ELISA, elevated levels of mucosal secretory IgA (SIgA) and plasma IgG antibody (Ab) responses were noted in aged mouse recipients. When cytokine production was examined, OVA-stimulated Peyer’s patch CD4+ T cells produced increased levels of IL-4. Further, CD4+ T cells from the lamina propria revealed elevated levels of IL-4 and IFN-γ production. In contrast, aged mice without AMSC transfer showed essentially no OVA-specific mucosal SIgA or plasma IgG Ab or cytokine responses. These results suggest that AMSCs can restore impaired mucosal immunity in the GI tract of aged mice.

Caloric restriction responses can maintain immune responses during aging (47.14)

Abstract Age-related defects accumulate in both the innate and adaptive arms of immunity to generate a state of immune deficiency. Our laboratory has previously shown a decrease in immune responses in aged mice compared to younger mice in the context of OX40 costimulation. This loss of immunity during aging underscores the need for simple approaches to boost immunity in older individuals. We hypothesize that immune responses in the context of OX40 activation or blockade of CTLA-4 in older mice can be restored and/or maintained through caloric restriction (CR) or dietary supplementation with a CR mimetic. Two CR dietary regimens were used to determine if immunity in old immune-compromised mice could be restored and if immunity could be maintained during aging. In addition mice were fed diets that were formulated with resveratrol (100 ppm), a CR mimetic. Tumor immune responses and Ag-specific T cell responses in these mice were then assessed and compared to young mice and the appropriate dietary controls. Our results demonstrate that caloric restriction cannot restore immune function in old mice. However, CR or resveratrol dietary supplementation initiated at a young age can maintain both OX40-mediated anti-tumor immunity and T cell responses as these mice age. Thus, the induction of a caloric restriction response (via traditional CR or by a CR mimetic) appears to maintain immunological fitness and may increase the effectiveness of immune-based cancer therapies in older subjects.

Immunomodulatory Effects of Dietary Supplementation with a Milk-Based Wolfberry Formulation in Healthy Elderly: A Randomized, Double-Blind, Placebo-Controlled Trial

Wolfberry (fruit of Lycium barbarum) has been prized for many years in China for its immunomodulatory property and its high specific antioxidant content. However, clear clinical evidence demonstrating the effect of wolfberry dietary supplementation is still lacking. After our earlier report showing that a proprietary milk-based wolfberry formulation (Lacto-Wolfberry) enhances in vivo antigen-specific adaptive immune responses in aged mice, the present study aimed at demonstrating the effect of dietary Lacto-Wolfberry supplementation on immune functions in the elderly, especially vaccine response known to decline with aging. A 3-month randomized, double-blinded, placebo-controlled study was conducted on 150 healthy community-dwelling Chinese elderly (65-70 years old) supplemented with Lacto-Wolfberry or placebo (13.7 grams/day). Immune response to influenza vaccine was assessed in the study, along with inflammatory and physical status. No serious adverse reactions were reported during the trial, neither symptoms of influenza-like infection. No changes in body weight and blood pressure, blood chemistry or cells composition, as well as autoantibodies levels were observed. The subjects receiving Lacto-Wolfberry had significantly higher postvaccination serum influenza-specific immunoglobulin G levels and seroconversion rate, between days 30 and 90, compared with the placebo group. The postvaccination positive rate was greater in the Lacto-Wolfberry group compared to the placebo group, but did not reach statistical significance. Lacto-Wolfberry supplementation had no significant effect on delayed-type hypersensitivity response and inflammatory markers. In conclusion, long-term dietary supplementation with Lacto-Wolfberry in elderly subjects enhances their capacity to respond to antigenic challenge without overaffecting their immune system, supporting a contribution to reinforcing immune defense in this population.

Th2 Immune Responses and Alternatively Activated Macrophages (AAMacs) in Helminth Infection in Aged Mice

This study aims to understand Th2 immune responses and alternative macrophage activation against nematode parasites in aged mice. Eighteen-month (18 M) and three-month (3 M) old C3H/HeN mice were inoculated with Heligmosomoides polygyrus (Hp) larvae. Real-time PCR analysis indicated that interleukin (IL)-4 and IL-13 gene expression was elevated in both groups after infection, but the expression level was significantly low in 18 M mice. Macrophage phenotype was monitored by measuring arginase-1 gene expression and immunofluorescence staining in small intestine, showing a decrease in the number of alternatively activated macrophages (AAMacs) around worm cysts in 18 M mice. These results suggest that the Th2 immune response in aged mice against a nematode parasite was not sufficiently induced to promote AAMacs.

Mucosal adjuvant activity of flagellin in aged mice

We evaluated the ability of flagellin, a highly effective mucosal adjuvant in mice and non-human primates, to promote mucosal innate and adaptive immunity in aged mice. We found that intratracheal instillation of flagellin induced a stronger respiratory innate response in aged mice than in young mice, and that intranasal instillation of flagellin was equally effective at triggering recruitment of T and B lymphocytes to the draining lymph nodes of young and aged mice. Intranasal immunization of aged mice with flagellin and the Yersinia pestis protein F1 promoted specific IgG and IgA production, but at lower levels and lower avidities than in young mice. Although intranasal instillation of flagellin and F1 antigen increased germinal center formation and size in young mice, it did not do so in aged mice. Our findings are consistent with the conclusion that flagellin can promote adaptive immune responses in aged mice, but at a less robust level than in young mice.

Effect of Lactobacillus johnsonii La1 on immune function and serum albumin in aged and malnourished aged mice

Objective Protein-energy malnutrition (PEM) is a serious nutritional problem that causes immune dysfunction in elderly people. Probiotic lactic acid bacteria may potentially modify immunity; however, there is little evidence to elucidate the influence of these bacteria on PEM in the elderly. Methods The immune modulation effects of lactic acid bacterium Lactobacillus johnsonii La1 (La1) were examined in aged mice and aged mice with PEM. Twenty-month-old male 57BL6/n mice ( n = 28) were divided into four groups and received the following diet for 14 d: a complete diet (20% protein) without Lal (control) or with Lal or a low-protein diet (5% protein) to induce PEM, with or without La1. All mice were immunized with diphtheria toxin (DT) with alfacalciferol at 7 d and sacrificed 14 d after starting the experimental diets. Results Serum albumin concentrations and body weight, both of which were reduced by the low-protein diet, were ameliorated by La1 intake and were the same as in mice receiving the control diet. Anti-DT immunoglobulin (Ig) A in fecal extract was increased by La1 intake in mice receiving the complete and low-protein diets. Serum anti-DT IgA, IgG, splenocyte proliferation, and CD8 + T cells were reduced by the low-protein diet and restored by La1 intake. Conclusion La1 enhances intestinal IgA production and helps recover nutritional status and systemic immune responses in aged mice with PEM. It is possible that La1 may contribute to immune system recovery in immunocompromised hosts such as elderly humans with PEM.

A Low Blood Ethanol Level Is Associated with Improved Cytokine Production in Aged Mice after Traumatic Injury

Many trauma patients have been consuming alcohol at the time of injury. Although high concentrations of alcohol are correlated with poor outcome, few studies have examined the effects of low levels of alcohol. We examined the effects of low alcohol exposure after burn injury using a murine model. Three- and 18-month-old mice were given ethanol or saline 30 minutes before a 15% total body surface area burn injury. Twenty-four hours after injury, cellular immune responses, including delayed-type hypersensitivity response and splenocyte proliferation were examined, along with production of interferon-gamma, interleukin (IL)-2, and IL-4. Alcohol administration resulted in a significant increase in interferon-gamma in the aged, but not young, burn-injured mice. Likewise, slight increases in IL-2, IL-4, and the delayed-type hypersensitivity response were observed. Low levels of ethanol at the time of injury are associated with partial restoration of immune responses in aged mice.