Response In Immunosuppressed Mice Research Articles

Effects of Low Molecular Weight Peptides from Red Shrimp (Solenocera crassicornis) Head on Immune Response in Immunosuppressed Mice.

This study aimed to investigate the immunoenhancement effects of low molecular weight peptides (SCHPs-F1) from red shrimp (Solenocera crassicornis) head against cyclophosphamide (CTX)-induced immunosuppressed mice. ICR mice were intraperitoneally injected with 80 mg/kg CTX for 5 consecutive days to establish the immunosuppressive model and then intragastrically administered with SCHPs-F1 (100 mg/kg, 200 mg/kg, and 400 mg/kg) to investigate its improving effect on immunosuppressed mice and explore its potential mechanism using Western blot. SCHPs-F1 could effectively improve the spleen and thymus index, promoting serum cytokines and immunoglobulins production and upregulating the proliferative activity of splenic lymphocytes and peritoneal macrophages of the CTX-treated mice. Moreover, SCHPs-F1 could significantly promote the expression levels of related proteins in the NF-κB and MAPK pathways in the spleen tissues. Overall, the results suggested that SCHPs-F1 could effectively ameliorate the immune deficiency caused by CTX and had the potential to explore as an immunomodulator in functional foods or dietary supplements.

Effects of low molecular weight peptides from monkfish (Lophius litulon) roe on immune response in immunosuppressed mice.

This study aimed to investigate the immunomodulatory activation of low-molecular-weight peptides from monkfish (Lophius litulon) roe (named MRP) on cyclophosphamide (CTX)-induced immunosuppressed mice. Our results indicated that MRP (100 mg/kg/d BW) could significantly increase the body weight and immune organ index, and improve the morphological changes in the spleen and thymus of mice. These effects subsequently enhance the serum levels of interleukin (IL)-6, IL-1β, tumor necrosis factor (TNF)-α, and immunoglobulin (Ig) A, IgM, and IgG. Furthermore, MRP could also improve CTX-induced oxidative stress, and activate the NF-κB and MAPK pathways in the spleen tissues. The findings reported herein indicate that MRP has a good immunomodulatory activation toward immunosuppressed mice, hence can potentially be developed as an immune adjuvant or functional food.

Jianqu fermentation with the isolated fungi significantly improves the immune response in immunosuppressed mice

Ethnopharmacological relevanceJianqu, a classical formula of traditional Chinese medicine, is used clinically to treat symptoms like chill and fever headache, diarrhea and loss of appetite and act on patients with low immunity. However, the quality control of Jianqu fermentation is not well established, and its function in regulating the body's immunity still remains unclear. Aim of the studyThe present study firstly assesses the structure and diversity of fungal community during Jianqu fermentation and then investigates the immune regulating function of Jianqu extract in mouse model. Materials and methodThe high-throughput sequencing is conducted to analyze the diversity and distribution of fungal community during the fermentation process of Jianqu, and then fungi with a high frequency and relative abundance are isolated. The immunosuppressed mice are induced by using cyclophosphamide (CTX) and used to evaluate the immune regulating function of Jianqu extract from natural fermentation or directed fermentation, respectively. ResultsWith the fermentation, the diversity and distribution of fungal community significantly changed. The number of OTU (operational taxonomic unit) was gradually decreased from 223 ± 1 in the early phase to 201 ± 11 in the middle phase and to 175 ± 32 in the later phase of Jianqu fermentation. Generally, in genus level, Millerozyma, Debaryomyces and Rhizomucor showed a significant increase and became dominant in the mid or later phase of fermentation, while the Aspergillus displayed a decrease following the fermentation. However, Saccharomycopsis is a dominate species in surveyed samples. Next, six fungi strains with a high frequency and relative abundance, including Saccharomycopsis fibuligera, Millerozyma farinose, Hyphopichia burtonii, Rhizomucor pusillus, Lichtheimia ramosa, and Monascus purpureus, are isolated successfully. Interestingly, directed fermentation for Jianqu with the six isolated fungi strains could achieve similar morphological characteristics with the natural fermentation. Consistently, Jianqu extract from directed fermentation demonstrated a similar therapeutic effect on immune response as that of naturally fermented Jianqu. ConclusionsWe firstly showed the significant change of structural profiles of fungal communities during Jianqu fermentation, and successfully isolated six dominate fungi strains in Jianqu. Interestingly, directed fermentation for Jianqu with these isolated strains could achieve a similar morphological characteristics and immune-modulating function as natural fermentation. It was suggested that Jianqu fermentation with functional fungi instead of natural microbes provide a new approach for the improvement of the production and quality control of the traditional Chinese medicine of Jianqu.

Effect of Astragali Radix with different sulfur fumigation technologies on immune function in mice

To investigate the effect of Astragali Radix with different sulfur fumigation technologies on immune function in mice, and observe the effect of different Astragali Radix samples on carbon clearance in cyclophosphamide induced immunosuppressed mice, on immune organ weight in immunosuppressed mice and on delayed type hypersensitivity response (DTH) induced by 2,4 dinitrochlorobenzene. Carbon clearance index, phagocytic index, organ index and ear swelling rate were taken as the indexes. The results showed that, all of the Astragali Radix with different sulfur fumigation technologies markedly increased the carbon clearance index K, phagocytic index α, immune organ weight and improved the ability of DTH response in immunosuppressed mice. As compared with the model group, combined hot air-microwave group had the most significant difference, but when other groups were compared with and combined hot air-microwave group, only carbon clearance test had significant difference. From the perspective of pharmacodynamics, the effect of Astragali Radix with different sulfur fumigationon technologies on the immune function of mice was investigated, which provided a reference for the selection of appropriate alternative technology, and also provided guidance for clinical medication.

Dehydroepiandrosterone and metyrapone partially restore the adaptive humoral and cellular immune response in endotoxin immunosuppressed mice

Prior exposure to endotoxins renders the host temporarily refractory to subsequent endotoxin challenge (endotoxin tolerance). Clinically, this state has also been pointed out as the initial cause of the non-specific humoral and cellular immunosuppression described in these patients. We recently demonstrated the restoration of immune response with mifepristone (RU486), a receptor antagonist of glucocorticoids. Here we report the treatment with other modulators of glucocorticoids, i.e. dehydroepiandrosterone (DHEA), a hormone with anti-glucocorticoid properties, or metyrapone (MET) an inhibitor of corticosterone synthesis. These drugs were able to partially, but significantly, restore the humoral immune response in immunosuppressed mice. A significant recovery of proliferative responsiveness was also observed when splenocytes were obtained from DHEA- or MET-treated immunosuppressed mice. In addition, these treatments restored the hypersensitivity response in immunosuppressed mice. Finally, although neither DHEA nor MET improved the reduced CD4 lymphocyte count in spleen from immunosuppressed mice, both treatments promoted spleen architecture reorganization, partially restoring the distinct cellular components and their localization in the spleen. The results from this study indicate that DHEA and MET could play an important role in the restoration of both adaptive humoral and cellular immune response in LPS-immunosuppressed mice, reinforcing the concept of a central involvement of endogenous glucocorticoids on this phenomenon.

Immunostimulating Effect of Aqueous Extract of <em>Amphypterygium Adstringens</em> on Immune Cellular Response in Immunosuppressed Mice

Amphypterygium adstringens is a Mexican tree known as cuachalalate whose bark is habitually used for the treatment of fresh wounds, gastric ulcers, gastrointestinal cancer and various inflammatory conditions. The aim of this study was to evaluate the immunostimulant effect of the aqueous extract of A. adstringens on immune cellular response in immunosuppressed mice. An aqueous extract from the bark of cuachalalate was administered into BALB/c mice for 10 days. We assessed their immunostimmulant activity on cellular immune response by Delayed Type Hypersensitivity Response (DHT) to dinitrofluorobencene (DNFB) and by MTT assay. L5178Y lymphoma was used as immunossuppression model. An increase in DHT was observed after treatment with 10 and 100 mg/kg of the aqueous extract from A. adstringens oral treatment in lymphoma bearing mice. Splenocyte proliferation rate was significantly increased (2.5 time) in immunosuppresed mice treated with 10 mg/kg oral treatment compared with group that received vehicle only. The present study showed for the first time the aqueous extract from A. adstringens as a positive immunostimulant agent in lymphoma bearing mice and we demonstrated evidence to support the traditionally use of cuachalalate in conditions in which the immune system is depressed.

Restoration of immune system function is accelerated in immunocompromised mice by the B-cell-tropic isoxazole R-11

BackgroundRestoration of impaired immune response in immunocompromised patients is a crucial problem. In this study we evaluated the efficacy of isoxazole R-11 in reconstitution of the immune response in immunosuppressed mice. MethodsMice were given a sublethal dose (250mg/kg b.w.) of cyclophosphamide (CP). The cellular immune response to ovalbumin (OVA) and the humoral immune response to sheep erythrocytes (SRBC) were generated. R-11 was administered at repetitive, intraperitoneal doses (20μg/mouse) until determination of the immune responses: 7 and 15 doses on alternate days for cellular and humoral immune response, respectively. For phenotypic studies R-11 was given per os, at a single dose of 20μg/mouse. The ability of R-11 to affect interleukin- 6 (IL-6) production was determined in the whole human blood cell culture. ResultsR-11 increased the content of CD19+ cells in the spleens and lymph nodes with a concomitant decrease of CD3+ and CD4+cells. The compound significantly accelerated restoration of both cellular and humoral immune responses, elevated the numbers of circulating leukocytes and splenocytes and normalized the blood cell picture. Supplementary experiments showed that R-11 was not toxic with regard to human peripheral blood mononuclear cells (PBMC) and that it upregulated IL-6 production in blood cell culture stimulated with lipopolysaccharide (LPS). ConclusionsWe demonstrated that R-11 is likely a B-cell tropic agent which can restore both cellular and humoral immune responses in immunocompromised mice and may have a potential to be applied in therapy of immunocompromised patients.

Immunomodulatory activity ofZingiber officinaleRoscoe,Salvia officinalisL. andSyzygium aromaticumL. essential oils: evidence for humor- and cell-mediated responses

AbstractObjectivesThe immunomodulatory effect of ginger, Zingiber officinale (Zingiberaceae), sage, Salvia officinalis (Lamiaceae) and clove, Syzygium aromaticum (Myrtaceae), essential oils were evaluated by studying humor- and cell-mediated immune responses.MethodsEssential oils were administered to mice (once a day, orally, for a week) previously immunized with sheep red blood cells (SRBCs).Key findingsClove essential oil increased the total white blood cell (WBC) count and enhanced the delayed-type hypersensitivity (DTH) response in mice. Moreover, it restored cellular and humoral immune responses in cyclophosphamide-immunosuppressed mice in a dose-dependent manner. Ginger essential oil recovered the humoral immune response in immunosuppressed mice. Contrary to the ginger essential oil response, sage essential oil did not show any immunomodulatory activity.ConclusionsOur findings establish that the immunostimulatory activity found in mice treated with clove essential oil is due to improvement in humor- and cell-mediated immune response mechanisms.

Immunomodulatory activity of Zingiber officinale Roscoe, Salvia officinalis L. and Syzygium aromaticum L. essential oils: evidence for humor- and cell-mediated responses.

The immunomodulatory effect of ginger, Zingiber officinale (Zingiberaceae), sage, Salvia officinalis (Lamiaceae) and clove, Syzygium aromaticum (Myrtaceae), essential oils were evaluated by studying humor- and cell-mediated immune responses. Essential oils were administered to mice (once a day, orally, for a week) previously immunized with sheep red blood cells (SRBCs). Clove essential oil increased the total white blood cell (WBC) count and enhanced the delayed-type hypersensitivity (DTH) response in mice. Moreover, it restored cellular and humoral immune responses in cyclophosphamide-immunosuppressed mice in a dose-dependent manner. Ginger essential oil recovered the humoral immune response in immunosuppressed mice. Contrary to the ginger essential oil response, sage essential oil did not show any immunomodulatory activity. Our findings establish that the immunostimulatory activity found in mice treated with clove essential oil is due to improvement in humor- and cell-mediated immune response mechanisms.

Monoclonal antibodies from mice bearing human colorectal carcinoma xenografts.

We have examined the serological response in immunosuppressed mice bearing xenografts of the human colorectal carcinoma line HT29. The sera of such animals contain antibodies which bind to HT29 cell membrane components. This antibody activity was not completely absorbed by either human lymphocytes or red blood cells suggesting that at least part of this activity is directed against tumour-associated antigens. By fusing the spleens from tumour-bearing animals to an established myeloma line we were able to produce 34 monoclonal antibodies which bound to HT29 cells. The specificity of these antibodies in binding assays against membrane preparations from a variety of normal and malignant tissues and cell lines was determined. Twenty-seven bound to components present on both normal and malignant human cell membranes; 4 to tumour membranes only, whilst 3 bound specifically to membranes prepared from colorectal carcinoma tissue or cell lines. Thus despite immunosuppression the xenograft-bearing mouse was able to recognise a number of antigens present on the tumour surface.

Effect of cysteine ethylester hydrochloride (Cystanin) on host defense mechanisms (II): Restorative effects on the suppression of antibody production

The production of hemolytic plaque forming cells (HPFC) in the spleen of BALB/c mice immunized with sheep red blood cells was significantly inhibited by carrageenan treatment (0.3 mg/kg, i.p.; on days -3 and -1). Cysteine ethylester hydrochloride (ethylcysteine) restored the inhibition of the HPFC production by carrageenan treatment in a dose-dependent manner (10-100 mg/kg, p.o.). Ia positive cells (antigen-presenting cells) increased in the spleen adherent cells (SAC) obtained from immunized mice, whereas they decreased in the SAC obtained from carrageenan-treated mice. An increase of Ia positive cells occurred in the SAC of carrageenan-treated mice given ethylcysteine. Ethylcysteine (10-100 mg/kg, p.o.; on days -2 and -1) prevented both the suppression of the HPFC production and the decrease of the number of thymus lymphocytes and peripheral leukocytes induced by cyclophosphamide treatment (30 mg/kg, i.p.; on days -1 and 0). Lyt 1.2 positive cells (helper T cells) decreased in the spleen T cells of cyclophosphamide-treated mice, but increased in the spleen T cells from cyclophosphamide-treated mice give ethylcysteine. On the other hand, Thy 1.2 negative cells (B cells) did not increase in the spleen cells of cyclophosphamide-treated mice with or without ethylcysteine. These results suggest that ethylcysteine restores the immune response in immunosuppressed mice through the functions of macrophages and/or helper T cells.

Augmentation of the Antibody Response by Lipoic Acid in Mice II. Restoration of the Antibody Response in Immunosuppressed Mice

Lipoic acid (Lip) was examined for its effect on the in vivo antibody response in mice. It was found that Lip significantly restored the suppressed antibody response to sheep erythrocytes (SRBC) in cyclophosphamide-injected mice when it was orally administered at 25 mg/kg twice a day for 4 consecutive days after immunization. On the other hand, Lip-administration did not affect the antibody response in normal mice immunized with SRBC. Normal or cyclophos- phamide-treated mice were primed with horse erythrocytes (HRBC) and were given either sal ne or Lip for 3 consecutive days. HRBC-specific helper T cell activity of their spleen cells were compared by coculturing these cells with trini- trophenyl (TNP)-keyhole limpet hemocyanin-primed spleen cells in the presence of TNP-HRBC as the antigen. A significant restoration of the suppressed helper T cell activity was observed in the Lip-administered group. However, the helper T cell activity was not affected significantly by Lip-administration in normal mice. Lip could also partially restore the helper T cell activities that were suppressed by the treatment with hydrocortisone or X-ray irradiation.