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Marine algae are photosynthetic eukaryotic organisms that are widely used as sources of food, cosmetics, and drugs. However, their biological and immunological effects on immune cells have not been fully elucidated. To unravel their immunological activity and broaden their application, we generated antigen‐presenting cells (APCs), including dendritic cells (DCs) and macrophages, from mouse bone marrow cells and treated them with six different marine algae extracts (MAEs). We evaluated cell viability, activation marker expression, and pro‐inflammatory cytokine production by APCs after 2 days of MAE treatment. All six MAEs significantly induced cytokine production of APCs, among which Pyropia yezoensis (PY), Peyssonnelia caulifera (PC), and Meristotheca papulosa (MP) extracts exhibited the strongest effect. Cladophora wrightiana var. minor (CW) extract moderately upregulated cytokine levels but increased the expression of activation markers on DCs. Moreover, PY, PC, MP, Sargassum pectinifera (SP), and Caulerpa okamurae (CO) pre‐treated APCs effectively stimulated T‐cell proliferation and cytokine production. Furthermore, the mice injected with MAEs exhibited higher cytokine (TNF‐α, IL‐6, and IL‐1β) production as well as enhanced innate immune cell recruitment capacities (DCs, monocytes, neutrophils, and natural killer cells) in the peritoneal cavity of the mice compared to those of the non‐treated mice. Therefore, all MAEs exhibited immunostimulatory potential, with PY, PC, CW, and MP extracts being the most effective in stimulating immune responses and cell activation. To the best of our knowledge, this is the first study to determine the immunomodulatory activities of six MAEs both in vitro and in vivo. [ABSTRACT FROM AUTHOR]

Abstract Background Morinda citrifolia (Noni) is a plant that has long been used in various products such as foods and cosmetics. Although noni has been known to have immunostimulatory activity, detailed mechanism at the cellular level has not been fully elucidated yet. In this study, we focused on understanding as to how noni fruit can positively stimulate body’s immune responses. Methods To do this, an ethanol extract of noni fruit (Mc-fEE) was prepared and administered for 30 days to male C57BL/6 mice for in vivo experiment. NK cell activity and cytokine production level from Mc-fEE-treated mice were analyzed by flowcytometry, real-time PCR, and ELISA. Mc-fEE-triggered molecular events were detected from RAW264.7 cells and splenocytes using Western blotting and real-time PCR analyses. Results The mRNA expression levels of cytokines such as interleukin families, interferon (IFN)-β, and tumor necrosis factor (TNF)-α were increased by Mc-fEE treatment in vitro and in vivo. Western blotting analysis showed that the phosphorylation levels of nuclear factor (NF)-κB and activator protein (AP)-1 subunits these were enhanced in Mc-fEE-treated RAW264.7 cells. In addition, according to in vivo experiments, it was considered that Mc-fEE can increase the population of splenic NK cells and subsequent upregulation of their cytotoxic activity against YAC-1 cells, a T- cell lymphoma. Conclusion In this paper, we could confirm that Mc-fEE has remarkable immunostimulatory effects by activation and increase of the NK cell population.

Withania somnifera (L.) Dunal (Solanaceae) (also known as Ashwagandha) is a botanical drug that has been used for centuries to treat many chronic diseases like high blood pressure, arthritis, diabetes, Alzheimer’s disease, and depression. As many botanical drugs, w. Somnifera possesses anti-inflammatory, antioxidant, anticarinogenic, anti-diabetic, and anti-asthmatic properties. W. somnifera is often compared to the ginseng plant due to its ability to reduce stress, improve cognitive functions (e.g., memory), and promote a healthy immune system. It promotes immunomodulatory effects whose function is to balance the humoral and cellular responses of the adaptive immune system. The therapeutic effect of w. Somnifera is attributed to active ingredients like alkaloids, steroidal lactones (such as withanolides, withaferins), and steroidal saponins. Although w. Somnifera is safe and highly recommended for treating various diseases, the current knowledge and understanding of its operational mechanisms are limited. One of the proposed mechanisms states that w. Somnifera promotes cellular-mediated immunity or initiates chemical interactions that contribute to therapeutic effects. Withania somnifera has been shown to play a significant role in immunological diseases by modulating several cytokines, increasing T-cell proliferation and enhancing macrophages functions. In this review, we will discuss the latest therapeutic effects of w. Somnifera on a number of diseases through modulating immunological markers and which specific components of w. Somnifera induce these therapeutic activities. We will also focus on the chemical properties in w. Somnifera components and their immunomodulatory role in type 2 allergic diseases where type 2 inflammation is highly imbalanced.

Background: Complex Great Powerful Blend (GPB) (a great powerful blend) is a hot water extract of three well-known dried fruits: goji berry, mulberry, and jujube. These fruits have been used as food for a long time, and this article sought to confirm the immunostimulatory effects of Complex GPB. Materials and Methods: To do this, in vitro study using RAW264.7 cells and in vivo using normal mice were performed. Cytokine production and NK cell activity levels were measured by enzyme-linked immunosorbent assay, real-time polymerase chain reaction (PCR), and the YAC-1 cell-killing assay. Transcription factor activation levels were also determined by western blotting analysis. Results: First, it was confirmed that Complex GPB had no cytotoxic effects on the cells and increased the production levels of tumor necrosis factor (TNF)-a in a concentration-dependent manner. Additionally, Complex GPB enhanced pro-inflammatory cytokine expressions such as TNF-a, IL-12a, and IL-1b. Western blotting analysis revealed that activation of the NF-kB and AP-1 pathways are involved. Furthermore, in vivo study confirmed that TNF-a was found to be elevated in the serum and splenocytes of mice-fed Complex GPB. Cytotoxic activation of NK cells was also increased in mice injected with Complex GPB. Conclusion: These results suggest that Complex GPB has an immune-enhancing effect, which can be used for immunomodulatory remedies. [ABSTRACT FROM AUTHOR]

Background: Morinda citrifolia (Noni) is a plant that has long been used in various products such as foods and cosmetics. Although noni has been known to have immunostimulatory activity, detailed mechanism at the cellular level has not been fully elucidated yet. In this study, we focused on understanding as to how noni fruit can positively stimulate body's immune responses. Methods: To do this, an ethanol extract of noni fruit (Mc-fEE) was prepared and administered for 30 days to male C57BL/6 mice for in vivo experiment. NK cell activity and cytokine production level from Mc-fEE-treated mice were analyzed by flowcytometry, real-time PCR, and ELISA. Mc-fEE-triggered molecular events were detected from RAW264.7 cells and splenocytes using Western blotting and real-time PCR analyses. Results: The mRNA expression levels of cytokines such as interleukin families, interferon (IFN)-β, and tumor necrosis factor (TNF)-α were increased by Mc-fEE treatment in vitro and in vivo. Western blotting analysis showed that the phosphorylation levels of nuclear factor (NF)-κB and activator protein (AP)-1 subunits these were enhanced in Mc-fEE-treated RAW264.7 cells. In addition, according to in vivo experiments, it was considered that Mc-fEE can increase the population of splenic NK cells and subsequent upregulation of their cytotoxic activity against YAC-1 cells, a T- cell lymphoma. Conclusion: In this paper, we could confirm that Mc-fEE has remarkable immunostimulatory effects by activation and increase of the NK cell population. [ABSTRACT FROM AUTHOR]

Crude exopolysaccharides from extracellular polymeric substances produced by the marine bacterium Bacillus sp. H5 were fractionated using DEAE-Sepharose FF and Sephadex G-75 chromatography. The high molecular weight fraction (89.0 kD) from the neutral fraction was designated EPS5SH; it contained mannose, glucosamine, glucose, and galactose in a molar ratio of 1.00: 0.02: 0.07: 0.02. Infra-red, gas chromatography–mass spectrometry, electrospray ionisation-tandem mass spectrometry analysis and nuclear magnetic resonance revealed EPS5SH was a mannan with α-(1 → 4)-Man p , α-(1 → 2)-Man p , α-(1 → 4, 6)-Man p and β-terminal-Man p. Preliminary in vitro experiments revealed that EPS5SH significantly upregulated nitric oxide synthesis and release of pro-inflammatory factors in murine macrophage RAW264.7 cells. Western blot experiments verified the immunostimulatory effects of EPS5SH through the modulation of the NF-κB and MAPK signalling pathways. In conclusion, EPS5SH was a novel immunostimulatory mannan. [ABSTRACT FROM AUTHOR]

The biological activities of water‐soluble components of edible mushroom Rubinoboletus ballouii (RB) were seldom reported. Polysaccharides of RB (RBP) were prepared and well‐characterized using chemical analyses. The immunomodulatory properties of RBP were investigated using human monocyte‐derived dendritic cells (moDC) in vitro, and cyclophosphamide (CTX)‐induced immunosuppressive mouse model. Results showed that RBP was found to contain 80.6% (w/w) of neutral sugars including D‐fucose, D‐mannose, D‐glucose and D‐galactose (1.7:1.4:1.0:1.8), and 12.5% (w/w) of proteins, which composed of glutamine, threonine, serine, etc. RBP could promote the maturation of moDC and increase the secretion of IL‐12p40, IL‐10, and TNF‐α. Furthermore, the stimulation of IL‐12p40 production was inhibited by pretreatment with toll‐like receptor (TLR)‐4 blocker or NF‐κB pathway blocker, suggesting that the activation of moDC by RBP was mediated through NF‐κB pathway via TLR‐4 receptor. On the other hand, in CTX‐treated mice, RBP restored the loss of CD34brightCD45dim hematopoietic stem cells and increased IL‐2 production in sera and splenocytes culture supernatant, as well as up‐regulated the percentage of CD4+ T helper lymphocyte in mice splenocytes. These findings strongly suggested that RBP are the active ingredients of RB responsible for its immunostimulatory actions and deserved to be further investigated as cancer supplements. [ABSTRACT FROM AUTHOR]

A number of immunostimulant effects of herbal medicines have been reported; however, the underlying mechanisms of their immunostimulatory effects have not been elucidated in detail. Our previous study showed that sugar-based nanoparticles derived from cell walls acted as the immunostimulatory component of boiled Glycyrrhizae radix water extracts. Therefore, the aim of the present study was to clarify the molecular mechanisms by which these cell wall-based nanoparticles functioned as immunostimulants. Mouse macrophage RAW-blue cells were stimulated by these nanoparticles and several immunological effects were investigated. When phosphorylation of nuclear factor-κB (NF)-κB p65 subunit was increased, the expression of the inflammatory cytokines interleukin-6 and tumor necrosis factor-α were induced via NF-κB. On the other hand, Toll-like receptor 4 recognizes cell wall components of bacteria and fungi. In the present study, it was also shown that these cell wall-based nanoparticles serve an immunostimulatory role as ligands of Toll-like receptor 4 by RNA interference experiments. The results of the present study suggested that the signaling pathway of nanoparticles obtained from boiled Glycyrrhizae radix water extracts, at least partially involved TLR4 and downstream signaling from this receptor, resulting in the immunostimulatory effects of these nanoparticles in RAW-blue cells. [ABSTRACT FROM AUTHOR]

Background: Radix Astragali is an herb with tonifying qi or adaptogenic effects and commonly used for spleen-qi deficiency in traditional Chinese medicine. Astragalus polysaccharides (APS) is one of the major bioactive ingredients, and little is known on APS in attenuating the dampness stagnancy due to spleen deficiency (DSSD). Objective: The objective of the study is to investigate the potential mechanism of action of APS underlying attenuating water and fluid retention of rats with the DSSD syndrome in order to provide novel insights into the application of APS on modulating the DSSD syndrome. Materials and Methods: Four-week-old Wistar rats were fed with one high-fat and low-protein diet and subjected to exhaustive swimming to induce the DSSD model for 8 weeks. APS (300, 600, and 1200 mg/kg) and Shen Ling Bai Zhu San (SLBZS) (2.5 g/kg) were administrated starting at 9 weeks for 2 weeks. Results: APS increased the body weight, decreased the water load index, and attenuated symptoms of the DSSD syndrome. APS also increased spleen and thymus indices, the percentage of CD3+, the percentage of CD3+ CD4+, and CD3+ CD4+ to CD3+ CD8+ ratio and decreased levels of serum interleukin (IL)-6, IL-10, and tumor necrosis factor-α in DSSD rats. Significant effects were seen for toll-like receptor 4 (TLR4) at both protein and gene expression levels with amelioration of expression levels in APS groups. Conclusion: These findings suggest that APS may be used to attenuate the fluid retention of the DSSD syndrome through the immunoregulatory effect, which is driven in part by the modulation of TLR4. [ABSTRACT FROM AUTHOR]

Highlights • The neutral fraction of flaxseed gum (NFG) was a xylose rich heteroglycan. • NFG showed immunostimulatory effects through TLR2 engagement. • MAPKs of JNK and P38 were activated by NFG with nuclear factor-κB be stimulated. Abstract Immunostimulatory activity of the flaxseed gum neutral fraction (NFG) was investigated. NFG was characterized as a xylose rich heteroglycan through monosaccharide composition analysis, FT-IR, methylation/GC–MS, and 1D/2D-NMR. NFG stimulated NO production and phagocytic activity of macrophages. Secretion of interleukin-6, interleukin-1β, and tumor necrosis factor-α (254.7 pg/mL, 2.5 ng/mL, and 42.9 pg/mL, respectively) was significantly induced by NFG. Mitogen-activated protein kinases of JNK and P38 were activated by NFG with increased phosphorylation of JNK and P38, while NO production was reduced to 6.05 and 4.42 μM by JNK and P38 inhibitor, respectively. Nuclear factor-κB signaling pathway was also activated by NFG with the suppression of IκBα and up-regulation of phosphorylation of IκBα and nuclear factor-κB P65. Toll like receptor-2 was the molecular target of NFG and responsible for the activation of down-stream signaling pathways. Thus, NFG from flaxseed gum may potentially be used as a natural immunomodulator in functional foods. [ABSTRACT FROM AUTHOR]

The immunostimulatory effects of Rhodomyrtus tomentosa leaf extract were evaluated in rainbow trout through changes in expression profile of genes involved in innate immune and antioxidant response, hematology and stress indicators. The concentrations of R. tomentosa at 10 and 100 μg per fish were administrated by intraperitoneal injection, alone or in combination with LPS. After 6 h of administration, the gene expression was measured in head kidney, spleen, and intestine. Results indicated that R. tomentosa exerted immunostimulatory effects by inducing the expression of il10 , saa , hepcidin , and sod in head kidney and the expression of il10 , tgfβ , and inos in intestine. In combination with LPS, the plant suppressed the expression of pro-inflammtory cytokine il1β , il8 and other consisting of saa and gpx1 in head kidney and il1β in spleen, pointing out its anti-inflammatory activities. Furthermore, the plant did not exert any impact on hematological parameters, but it was able to reduce cortisol levels when co-administered with LPS, indicating that R. tomentosa could attenuate stress response in rainbow trout. Our observations suggest that R. tomentosa induced the expression of genes involved in cytokine and innate immune response and modulated the physiological stress response as indicated by the suppressed cortisol in rainbow trout. [ABSTRACT FROM AUTHOR]

To effectively reverse multiple drug resistance (MDR) in tumor treatments, a functional nano-sized drug delivery system with active targeting function and pH sensitivity was prepared for the co-delivery of multiple drug resistance inhibitors. Buthionine sulfoximine (BSO) to inhibit GSH synthesis and celecoxib (CXB) to down-regulate P-gp expression were co-loaded in polymer/inorganic hybrid nanoparticles to form buthionine sulfoximine/celecoxib@biotin-heparin/heparin/calcium carbonate/calcium phosphate nanoparticles (BSO/CXB@BNP). To investigate the reversal of MDR, the drug resistant cells (MCF-7/ADR) were pretreated by the dual-inhibitor loaded nanoparticles (BSO/CXB@BNP) followed by the treatment of doxorubicin (DOX) loaded nanoparticles (DOX@BNP). The dual-inhibitor loaded nanoparticles (BSO/CXB@BNP) exhibited greatly enhanced efficiency in down-regulation of GSH and P-gp since BSO and CXB had combined effects on the reduction of GSH and P-gp in drug resistant tumor cells. As a result, BSO/CXB@BNP exhibited a significantly improved capability in reversal of MDR compared with mono-inhibitor loaded nanoparticles (CXB@BNP and BSO@BNP). As compared with free drug resistance inhibitors, delivery of drug resistance inhibitors by functional nanocarriers could obviously improve the therapeutic efficiency due to enhanced cellular uptake and increased intracellular drug accumulation. The study on immunostimulatory effects of different treatments showed that BSO/CXB@BNP treatment resulted in the lowest concentration of interleukin 10, a cytokine related to tumor development. These results suggest the nanoparticulate drug delivery platform developed in this study has promising applications in multiple drug delivery to overcome drug resistance in tumor treatments. [ABSTRACT FROM AUTHOR]

In an attempt to discover a new synthetic vaccine adjuvant, the glycosylation of hederagenin, gypsogenin, and oleanolic acid acceptors with di- and trisaccharide donors to generate a range of mimics of natural product QS-21 was carried out. The saponins were formulated with phosphatidylcholine and cholesterol, and the structures analyzed by transmission electron microscopy. 3-O-(Manp(1→3)Glcp)hederagenin was found to produce numerous ring-like micelles when formulated, while C-28 choline ester derivatives preferred self-assembly and did not interact with the liposomes. When alone and in the presence of cholesterol and phospholipid, the choline ester derivatives produced nanocrystalline rods or helical micelles. The effects of modifying sugar stereochemistry and the aglycone on the immunostimulatory effects of the saponins was then evaluated using the activation markers MHC class II and CD86 in murine bone marrow dendritic cells. The most active saponin, 3-O-(Manp(1→3)Glcp)hederagenin, was stimulatory at high concentrations in cell culture, but this did not translate to strong responses in vivo. [ABSTRACT FROM AUTHOR]

Withania somnifera (L.) Dunal (Solanaceae) (also known as Ashwagandha) is a botanical drug that has been used for centuries to treat many chronic diseases like high blood pressure, arthritis, diabetes, Alzheimer's disease, and depression. As many botanical drugs, w. Somnifera possesses anti-inflammatory, antioxidant, anticarinogenic, anti-diabetic, and anti-asthmatic properties. W. somnifera is often compared to the ginseng plant due to its ability to reduce stress, improve cognitive functions (e.g., memory), and promote a healthy immune system. It promotes immunomodulatory effects whose function is to balance the humoral and cellular responses of the adaptive immune system. The therapeutic effect of w. Somnifera is attributed to active ingredients like alkaloids, steroidal lactones (such as withanolides, withaferins), and steroidal saponins. Although w. Somnifera is safe and highly recommended for treating various diseases, the current knowledge and understanding of its operational mechanisms are limited. One of the proposed mechanisms states that w. Somnifera promotes cellular-mediated immunity or initiates chemical interactions that contribute to therapeutic effects. Withania somnifera has been shown to play a significant role in immunological diseases by modulating several cytokines, increasing T-cell proliferation and enhancing macrophages functions. In this review, we will discuss the latest therapeutic effects of w. Somnifera on a number of diseases through modulating immunological markers and which specific components of w. Somnifera induce these therapeutic activities. We will also focus on the chemical properties in w. Somnifera components and their immunomodulatory role in type 2 allergic diseases where type 2 inflammation is highly imbalanced., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Alanazi and Elfaki.)

Lupinus angustifolius (blue lupin) is produced abundantly in Australia and used mainly as animal feed. However, these seeds have excellent nutritional value with high protein, high dietary fibre and low fat content with a huge potential for value addition. In the present study, blue lupin polysaccharides have been isolated and their biological activities investigated. Hot water extraction and size-exclusion chromatography yielded six polysaccharide fractions that have been designated as BLP-1, BLP-2, BLP-3, BLP-4, BLP-5 and BLP-6 . Gas chromatography was employed to determine the mono-sugar compositions of these fractions which showed the existence of galactose, fucose, rhamnose, glucose, mannose, ribose and xylose. The antioxidant activities of all the fractions were investigated using ABTS + * radical scavenging activity and ferrous chelating activity. Immunostimulatory activities of these fractions were measured by treating the mouse macrophages (RAW 264.7) and monitoring the production of nitric oxide (NO) by Griess reagent method. Three of the blue lupin polysaccharides (BLP-1, BLP-2 and BLP-5) displayed significant antioxidant activities. Some of the fractions have effectively stimulated mouse macrophages in a concentration-dependent manner indicating their immunostimulatory capability. FT-IR spectroscopic technique was employed for a preliminary structural characterisation of the active polysaccharide fractions. [ABSTRACT FROM AUTHOR]

The objective of this study was to investigate the immunostimulatory effects of a polysaccharide fraction from the leaves of Diospyros kaki Thumb (PLE0) and the molecular mechanism responsible for its action in RAW 264.7 macrophages as well as in vivo effects on cyclophosphamide-induced immunosuppression in mice. PLE0 concentration-dependently activated the expressions of inducible nitric oxide synthase (iNOS) at the protein and mRNA levels and its promoter activity, and that these activations caused attendant increases the nitric oxide (NO) production. In addition, PLE0 increased the mRNA expressions of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and IL-6. Molecular data revealed that PLE0 increased the transcriptional activity and nuclear translocation of nuclear factor-κB (NF-κB) by inducing the degradation of inhibitory κBα (IκBα) and the phosphorylation of inhibitory κB kinase (IKK). Moreover, anti-toll-like receptor 2 (TLR2) antibody and myeloid differentiation primary response gene 88 (MyD88)-specific siRNA significantly reduce PLE0-induced NO production in RAW 264.7 macrophages. Pretreatment with PLE0 recovered cyclophosphamide-induced reductions in thymus and spleen indices as well as neutrophil counts. Taken together, our data suggest that PLE0 up-regulates the expressions of iNOS, TNF-α, IL-1β, and IL-6 genes by activating TLR2-mediated NF-κB activations, and that these actions are responsible for its immunostimulatory effects. [ABSTRACT FROM AUTHOR]

In spite that carotenoid-based sexual ornaments are one of the most popular research topics in sexual selection of animals, the antioxidant and immunostimulatory role of carotenoids, presumably signaled by these colorful ornaments, is still controversial. It has been suggested that the function of carotenoids might not be as an antioxidant per se, but that colorful carotenoids may indirectly reflect the levels of nonpigmentary antioxidants, such as melatonin or vitamin E. We experimentally fed male Iberian green lizards ( Lacerta schreiberi) additional carotenoids or vitamin E alone, or a combination of carotenoids and vitamin E dissolved in soybean oil, whereas a control group only received soybean oil. We examined the effects of the dietary supplementations on phytohaemagglutinin (PHA)-induced skin-swelling immune response and body condition. Lizards that were supplemented with vitamin E alone or a combination of vitamin E and carotenoids had greater immune responses than control lizards, but animals supplemented with carotenoids alone had lower immune responses than lizards supplemented with vitamin E and did not differ from control lizards. These results support the hypothesis that carotenoids in green lizards are not effective as immunostimulants, but that they may be visually signaling the immunostimulatory effects of non-pigmentary vitamin E. In contrast, lizards supplemented with carotenoids alone have higher body condition gains than lizards in the other experimental groups, suggesting that carotenoids may be still important to improve condition. [ABSTRACT FROM AUTHOR]

One hundred twenty-six day old broiler chicks were divided into three experimental groups A, B and C, each having 42 chicks per group. Group B was subdivided into 3 groups; y1, y2 and y3 each having 14 chicks per group and fed 50, 100 and 200 gm yogurt/kg of feed respectively. Similarly group C was subdivided into three groups; g1, g2 and g3 offered grinded garlic @ 10, 20 and 40gm garlic/kg of feed respectively. Group A was kept as a control and fed basal diet having no supplementation. Group y3 showed immense potential in increasing HI titer until last day of experiment but garlic showed no effect upon HI titer. The heterophils population and Heterophils/Lymphocyte (H/L) ratio was also improved in both yogurt and garlic supplemented groups, however g3 garlic fed group showed a better response in increasing heterophil population over the range of garlic fed groups.TLC remained normal in both yogurt and garlic fed groups throughout the experiment. It was concluded that both yogurt and garlic supplementations have beneficial effects to improve immunity. [ABSTRACT FROM AUTHOR]

Many investigators have studied the therapeutic and preventive effects of yogurt and lactic acid bacteria, which are commonly used in yogurt production, on diseases such as cancer, infection, gastrointestinal disorders, and asthma. Because the immune system is an important contributor to all of these diseases, an immunostimulatory effect of yogurt has been proposed and investigated by using mainly animal models and, occasionally, human subjects. Although the results of these studies, in general, support the notion that yogurt has immunostimulatory effects, problems with study design, lack of appropriate controls, inappropriate route of administration, sole use of in vitro indicators of the immune response, and short duration of most of the studies limit the interpretation of the results and the conclusions drawn from them. Nevertheless, these studies in toto provide a strong rationale for the hypothesis that increased yogurt consumption, particularly in immunocompromised populations such as the elderly, may enhance the immune response, which would in turn increase resistance to immune-related diseases. This hypothesis, however, needs to be substantiated by well-designed randomized, double-blind, placebo-controlled human studies of an adequate duration in which several in vivo and in vitro indexes of peripheral and gut-associated immune response are tested. [ABSTRACT FROM AUTHOR]