Cyclophosphamide-induced Immunosuppressed Mice Research Articles

Experimental sporotrichosis in a cyclophosphamide-induced immunosuppressed mice model.

This report describes a model of host resistance for Sporothrix schenckii, an opportunistic fungi in immunosuppressed mice with cyclophosphamide (CY) to be used in studies of immunotoxicology and immunopharmacology. Two doses of CY were administered intraperitoneally: 200mg/kg and a booster of 150mg/kg at 9-day intervals. Three days after the first dose of CY the animals were infected subcutaneously with 1.8 × 108 yeast/ml (S. schenckii ATCC 16345). At 7 and 14 days post-infection, the animals were euthanized and analyzed the fungal load by unit forming colony count in the spleen and popliteal lymph nodes. The relative weight of thymus and spleen, splenic index, the frequency of T and B cells in spleen by flow cytometry, the hind paw inflammation index and cytokine (interleukin [IL]-17, IL-10, and interferon [IFN]-γ) profile were measured. Histopathological studies of the spleen and the hind paw were also assessed. The immunosuppression status was confirmed at the evaluated days by reduction of relative weight of thymus, reduction of the splenic white pulp, the population of B and T lymphocytes, and the cytokine profile in the treated mice with CY in comparison with nontreated groups, associated to higher fungal load in hind paw and spleen in the infected mice. The described model reveals an increasing in susceptibility to infection and severity when associated with immunosuppression. This model can serve as a reference for studies of S. schenckii host resistance in pharmaceutical and toxicological studies.

Investigation of the immunomodulatory activity of Tricholoma matsutake mycelium in cyclophosphamide-induced immunosuppressed mice

Tricholomamatsutake, a popular food and biopharmaceutical resource in Asia, possesses various pharmacological activities. Although T. matsutake mycelium(TM) may enhance immunity, previous studies, to the best of our knowledge, have been performed on normal animals or cells alone. The present study aimed to evaluate the immunomodulatory activity of TM at doses of 0.3, 1.0 and 2.0g/kg in cyclophosphamide (CTX)‑induced immunosuppressed mouse models. TM treatment for 2weeks markedly improved the gain in bodyweight, increased organ indices, reduced hind paw swelling and positively regulated the cytotoxicity of natural killer cells and the proliferation of lymphocytes. These effects are similar to that of thymosin α1 (0.16mg/kg) which served as the positive control. In CTX‑induced immunosuppressed mice, TM demonstrated marked effects on the modulation of the production of immunoglobulin (Ig)G and IgA, and the levels of interleukin‑2, 6, 10 and 12, interferon‑α and γ and tumor necrosis factor‑α in serum. Compared with CTX mice, the reduced activity of nuclear factor (NF)‑κB in serum and spleen, and phosphorylation of inhibitor of NF‑κB kinase α/β in spleen were observed in TM‑treated mice. Taken together, TM effectively improved immune function in immunosuppressed mice via modulation of ILs and inflammatory factors associated with the NF‑κB signaling pathway.

Dietary Chlorella vulgaris Ameliorates Altered Immunomodulatory Functions in Cyclophosphamide-Induced Immunosuppressive Mice.

Based on the well-known toxicity of cyclophosphamide (CYP) on the immune system, this research investigated the modulating effects of the long-term dietary Chlorella vulgaris (CV) supplementation on the immunosuppression induced by CYP in mice, in order to provide a novel dietary design to mitigate the side effects of CYP therapy. Control, CYP-treated, CYP + CV (6%), CYP + CV (12%) and CYP + CV (24%) were used for 6 weeks, CV supplement in diet recovered the significantly reduced immunological function in CYP treated mice. As CV may have a modulating function through the inducible expression of cytokines, we assayed the expressions of interleukin-2 (IL-2), interleukin-12 (IL-12), tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ). Our results suggested that CYP significantly reduced the lymphocytes proliferation and phagocytic activities of macrophages, and stimulated the production of IL-2, IL-12, TNF-α and IFN-γ and that this impairment has been successfully adjusted by CV supplementation. Treatment with the algae also enhanced the natural killer (NK) cells cytotoxicity, and ameliorate histological changes of the spleen in CYP-treated mice. Therefore, as we found in this study, a diet supplemented with whole CV has beneficial effects on CVP-induced immunosuppression, through its immunomodulatory potential.

Alleviation of cyclophosphamide-induced immunosuppression in mice by naturally acetylated hemicellulose from bamboo shavings

ABSTRACTBamboo-shavings hemicellulose (BSH) is a water-extractable hemicellulose isolated from steamed-exploded bamboo shavings. The present study investigated the protective potential of BSH against cyclophosphamide (CPA)-induced immunosuppression in mice. Mice were orally administered BSH once daily at the dose of 50, 100 or 200 mg/kg body weight (BW) for 14 days, coupled with a hypodermic injection of CPA (70 mg/kg BW/day) on days 4, 8 and 12. The results showed that 14 days of oral administration of BSH at a dose of 100 or 200 mg/kg BW/day significantly accelerated the recoveries of serum hemolysin formation, phagocytic function of the reticuloendothelial system, splenocyte proliferation, splenic NK cell activity, secretion of splenic Th1/Th2 cytokines (IL-2, IL-12, TNF-α, INF-γ/IL-4) together with mRNA expression of Th1/Th2 transcription factors (T-bet/GATA-3) in CPA-induced immunosuppressive mice. Our results demonstrated that BSH could ameliorate CPA-induced immunosuppression in mice and may potentially serve as a supportive therapy in conventional chemotherapy.

Immunoenhancement of Edible Fungal Polysaccharides (Lentinan, Tremellan, and Pachymaran) on Cyclophosphamide-Induced Immunosuppression in Mouse Model.

Fungal polysaccharides display a variety of important biological activities, including anti-inflammatory, antitumor, and immune-stimulating activities. The aim of present study was to investigate the immunomodulatory effect of fungal polysaccharides on cyclophosphamide-induced immunosuppression in mice. Mice were pretreated orally with lentinan, tremellan, pachymaran, or a mixture of the three, respectively. The results showed that pretreatments with polysaccharides significantly increased the thymus index in cyclophosphamide-induced immunosuppression mice. The level of the cytokine IL-10 in sera of cyclophosphamide-induced mice was decreased after pretreatments of polysaccharides. Flow cytometry results showed that pretreatments with polysaccharides enhanced the phagocytosis of peritoneal macrophages in mice. The increased levels of serum antibody IgG and IgM were observed in the groups pretreated with polysaccharides. Our work demonstrated that the treatment of polysaccharides elicited strong immune activity and a protective effect against cyclophosphamide-induced immunosuppression.

Polysaccharide from wheat bran induces cytokine expression via the toll-like receptor 4-mediated p38 MAPK signaling pathway and prevents cyclophosphamide-induced immunosuppression in mice

ABSTRACTWheat bran-derived polysaccharides have attracted particular attention due to their immunomodulatory effects. However, the molecular mechanisms underlying their functions are poorly understood. The current study was designed to examine the effect of wheat bran polysaccharide (WBP) on RAW 264.7 cells and the underlying signaling pathways, which have not been explored. In addition, we also investigated the immuno-enhancement effects of WBP on cyclophosphamide (CTX)-induced immunosuppression in mice. WBP significantly increased the concentrations of intracellular nitric oxide (NO) and cytokines such as prostaglandin E2 (PGE2) and tumor necrosis factor-α (TNF-α) in RAW 264.7 cells. The result of RT-PCR analysis indicated that WBP also enhanced inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), and TNF-α expression. Further analyses demonstrated that WBP rapidly activated phosphorylated p38 mitogen-activated protein kinase (MAPK) and the transcriptional activities of activator protein-1 (AP-1) and nuclear factor (NF)-κB via toll-like receptor 4 (TLR4). Furthermore, in vivo experiments revealed that WBP increased the spleen and thymus indices significantly, and markedly promoted the production of the serum cytokines IL-2 and IFN-γ in CTX-induced immunosuppressed mice. Taken together, these results suggest that WBP can improve immunity by enhancing immune function, and could be explored as a potential immunomodulatory agent in functional food.

Investigation on Immunomodulatory Activity of Calf Spleen Extractive Injection in Cyclophosphamide-induced Immunosuppressed Mice and Underlying Mechanisms.

Calf spleen extractive injection (CSEI), extracted from the spleen of healthy cows (within 24h of birth), is a small peptides enriched extraction while the ratio between peptide and ribose is 76±15.2mg/μg. CSEI is usually used as an ancillary agent to assist cancer patients with immune dysfunction. The present study aims to evaluate the immunomodulatory activity of CSEI in cyclophosphamide (CTX)-induced mice model of immunosuppression and its underlying mechanisms. During the experiment, thymosin ɑ1 (0.16mg/kg) was served as the positive control drug. In CTX-induced immunosuppressed mice, CSEI significantly increased bodyweights and spleen indexes, and upgraded the natural killer activity together with lymphocytes proliferation. CSEI regulated the production of IgG and IgA, and the levels of IL-2, 6, 10, 12 and IFN-ɑ, γ and TNF-ɑ in serum of CTX-induced immunosuppressed mice. Furthermore, CSEI markedly downregulated nuclear factor kappa-B (NF-κB) expression which was controlled by IKKβ. Taken together, CSEI effectively improved immune function in CTX-induced immunosuppression related to NF-κB signalling pathway via regulating the production of immunoglobulins, interleukins and some inflammatory factors.

Exopolysaccharide fraction from Pediococcus pentosaceus KFT18 induces immunostimulatory activity in macrophages and immunosuppressed mice

Exopolysaccharide fraction from Pediococcus pentosaceus KFT18 (PE-EPS), a lactic acid bacteria isolated from Kimchi (a Korean fermented vegetable product), was preliminary characterized and its immunostimulating effects were analysed. In this study, we used interferon-γ (IFN-γ)-primed RAW 264·7 macrophages and CD3/CD28-stimulated splenocytes to determine the immunotimulatory activities of PE-EPS. Upon exposure to PE-EPS, IFN-γ-primed RAW 264·7 macrophages showed significant increases in the expressions of inducible nitric oxide synthase (iNOS), tumour necrosis factor-α (TNF-α), interleukin (IL)-6 and IL-1β. Molecular data using reporter gene assay and electrophoretic mobility shift assay (EMSA) revealed that PE-EPS upregulated transcriptional activity, DNA binding and the nuclear translocation of nuclear factor-κB (NF-κB). Furthermore, PE-EPS enhanced anti-CD3/CD28-specific proliferation and the productions of IL-2 and IFN-γ in primary splenocytes. In cyclophosphamide-induced immunosuppressed mice, pretreatment with PE-EPS (5, 15 or 45 mg kg(-1) day(-1), p.o.) increased thymus and spleen indices, and improved lymphocyte and neutrophil counts. PE-EPS stimulated the IFN-γ-primed macrophages and primary splenocytes to induce immune responses and improved the cyclophosphamide-induced immunosuppression in mice. The results in this study improved our understanding of immunostimulating activity of PE-EPS and supported its potential treatment option as a natural immunostimulant.

In Vitro and In Vivo Immunomodulatory Activity of Okra (Abelmoschus esculentus L.) Polysaccharides.

Crude okra (Abelmoschus esculentus L.) polysaccharide (RPS) was obtained by water extraction and alcohol precipitation. Three purified fractions of RPS, designated RPS-1, RPS-2, and RPS-3, were fractioned by diethylaminoethyl (DEAE)-cellulose chromatography. Their molecular weights, monosaccharide compositions, infrared (Fourier transform infrared [FT-IR]) spectra, and nuclear magnetic resonance (NMR) spectra were analyzed. Their immunomodulatory activity was evaluated with an in vitro cell model (RAW264.7 cells). In vivo immunomodulatory activity of RPS-2 was evaluated in normal and cyclophosphamide-induced immunosuppressed mice. The results showed that the molecular weights of RPS-1, RPS-2, and RPS-3 were 600, 990, and 1300 kDa, respectively. RPS-1 and RPS-2 were mainly composed of galactose, rhamnose, galacturonic acid, and glucuronic acid, while RPS-3 was mainly composed of galactose, rhamnose, galacturonic acid, glucuronic acid, and glucose. FT-IR and NMR spectrum data indicated a rhamnogalacturonan I characteristic of polysaccharide. Both RPS and its purified fractions RPS-1, RPS-2, and RPS-3 significantly increased RAW264.7 cell proliferation, nitric oxide (NO) production, inducible nitric oxide synthase (iNOS) expression, and tumor necrosis factor (TNF)-α, interferon (IFN)-γ, and interleukin (IL)-10 secretion (P < .05). The purified fraction RPS-2 also increased the spleen index, splenocyte proliferation, and cytokine secretion in vivo. These results indicate that okra polysaccharides may potentially serve as novel immunomodulators.

A comb-like branched β-d-glucan produced by a Cordyceps sinensis fungus and its protective effect against cyclophosphamide-induced immunosuppression in mice

An exopolysaccharide (EPS) was fractionated from fermentation media of a Cordyceps sinensis fungus (Cs-HK1) by ethanol precipitation at 2/5 volume ratio of ethanol/media. Its structural characteristics were elucidated by FT-IR, GC, GC–MS, 1D and 2D NMR combined with periodate oxidation, Smith degradation, partial acid hydrolysis, and methylation analysis. Furthermore, the immunomodulatory activity of EPS was evaluated by the model of cyclophosphamide-induced immunosuppression. The results from monosaccharide composition and partial acid hydrolysis indicated that EPS almost consisted of glucose excluding a trace amount of mannose. GC–MS and NMR analysis further confirmed EPS had a linear backbone of (1→3)-β-d-glucopyranosyl residues with a single (1→6)-β-d-glucopyranosyl side-branching unit for every three β-d-glucopyranosyl residues, showing a comb-like β-d-glucan with short and intensive branches, which was responsible for high viscosity. Moreover, EPS could significantly enhance immune organs and stimulate the release of major cytokines TNF-α and INF-γ, suggesting that EPS exhibited protective effect in immunocompromised mice.

Effects of Fuzheng Paidu tablet on peripheral blood T lymphocytes, intestinal mucosa T lymphocytes, and immune organs in cyclophosphamide-induced immunosuppressed mice

Objective: The aim of this study is to investigate the effects of a Fuzheng Paidu tablet on peripheral blood T lymphocytes, intestinal mucosa T lymphocytes, and immune organs in cyclophosphamide (CY)-induced immunosuppressed mice. Methods: The experimental mice (but not the control mice) were intraperitoneally injected with 80 mg/kg of CY solution every day for 3 consecutive days. Meanwhile, each mouse was administered with corresponding drugs for 7 continuous days. Then, 1 h after the last administration, each index was detected. Results: The Fuzheng Paidu tablet significantly increases the CD4+/CD8+ ratio (P < 0.01) and the number of CD3+ and CD4+ cells in immunosuppressed mice (P < 0.01). In addition, the tablet apparently enhances the CD3+, CD4+, and CD8+ levels in the intestinal mucosal immune system (P < 0.01) as well as reverses the reduction of spleen lymphoid nodules and lymphocytes (P < 0.01). It also significantly improves intestinal inflammation, thymic atrophy, and sparse thymocytes in immunosuppressed mice (P < 0.01). Discussion: The Fuzheng Paidu tablet greatly increases the levels of peripheral blood T lymphocytes and intestinal mucosal T lymphocytes as well as impoves atrophied thymuses and spleens in CY-induced immunosuppressed mice.

Immunostimulatory polysaccharide isolated from the leaves of Diospyros kaki Thumb modulate macrophage via TLR2

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.

Lactobacillus sakei K040706 evokes immunostimulatory effects on macrophages through TLR 2-mediated activation.

Lactobacillus sakei K040706 is the most populous lactic acid bacteria (LAB) in over ripened Doenjang, a traditional Korean fermented soybean paste. In this study, we investigated the immunostimulating effects of L. sakei K040706 (K040706) in macrophages and in cyclophosphamide-induced immunosuppressed mice. Upon exposure to K040706, significant increases in phagocytic activity and in the productions of nitric oxide (NO), tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) were observed in rIFN-γ-primed RAW 264.7 macrophages. K040706 also increased the expressions of inducible nitric oxide synthase (iNOS) at the protein and promoter binding levels, and the expressions of iNOS, TNF-α, and IL-6, at the mRNA level. In addition, K040706 significantly increased the transcriptional activities and DNA binding of nuclear factor-κB (NF-κB), which was accompanied by parallel enhancement of the nuclear translocation of p65 via the phosphorylations inhibitory kappa B-α (IκB-α) and IκB-kinase (IKK). On the other hand, pretreatment with NF-κB inhibitors reduced K040706-induced NO production in IFN-γ-primed RAW 264.7 macrophages. Furthermore, K040706 induced-NO production was completely abolished by anti-Toll-like receptor 2 (TLR2) antibody. In our cyclophosphamide-induced immunosuppressed mouse model, administration of K040706 restored thymus and spleen indices. Taken together, our findings suggest that K040706 improves immune function by regulating immunological parameters, such as, the productions of NO, TNF-α, and IL-6 via NF-κB activation, and by activating TLR2 in rIFN-γ-primed macrophages. In parallel, K040706 restored immunological parameters in cyclophosphamide-induced immunosuppressed mice and may warrant further evaluations as potential immunomodulatory agent.

Molecular mechanism underlying chemoprotective effects of Ganoderma atrum polysaccharide in cyclophosphamide-induced immunosuppressed mice

The molecular mechanism underlying the chemoprotective effects of Ganoderma atrum polysaccharide in cyclophosphamide-induced immunosuppressed mice was investigated. In Cy-treated mice, PSG-1 treatment significantly promoted the phagocytosis, and stimulated the production of NO and cytokines (TNF-α and IL-1β) in peritoneal macrophages. Moreover, PSG-1 elevated the phosphorylation of MAPKs and Akt, as well as expression of NF-κB in peritoneal macrophages. In addition, PSG-1 enhanced the recovery of T and B cell proliferation responses in Cy-treated mice. Furthermore, Ca2+ concentration and PKC activity of spleen lymphocytes in PSG-1 groups dramatically increased as compared with that of the model group. Finally, PSG-1 administration was found to dose-dependently improve the decline of cAMP level and PKA activity caused by Cy. These findings indicated that the chemoprotective effects of PSG-1 may be attributed to its capacity to activate peritoneal macrophages and spleen lymphocytes in Cy-treated mice.

Chronodependent effect of interleukin-2 on mouse spleen cells in the model of cyclophosphamide immunosuppression.

We studied the chronodependent effect of IL-2 in the experimental model of immunodeficiency, cyclophosphamide-induced immunosuppression in mice. IL-2 in a dose of 100 U/ mouse was administered at 10.00 and 16.00 for 3 days after injection of cyclophosphamide. In contrast to the morning treatment with the cytokine, evening administration produced antiapoptotic effect on splenocytes and stimulated proliferation to a greater extent. This was accompanied by an increase in the number of CD4(+), CD25(+) and CD4(+)25(+) cells in the spleen to a level of intact mice. More pronounced effect of the evening mode of IL-2 administration on the proliferation and subpopulation composition of mouse spleen cells in the studied model can be associated with high blood level of CD25(+) cells at this time of the day.

In vitro and in vivo immunostimulatory activity of an exopolysaccharide-enriched fraction from Bacillus subtilis.

The aim of this study was to investigate the immunostimulatory effects of an exopolysaccharide-enriched fraction obtained from Bacillus subtilis J92 (B-EPS). To determine the immunostimulatory activities of B-EPS, we used IFN-γ-primed RAW 264.7 macrophages and CD3/CD28-stimulated splenocytes. Increases in the levels of NO and many cytokines, such as, TNF-α, IL-6, and IL-1β, were observed in IFN-γ-primed RAW 264.7 macrophages by Griess reaction and ELISAs respectively. Using Western blotting and qRT-PCR, we found that B-EPS increased the protein and mRNA expressions of iNOS and the mRNA expressions of TNF-α, IL-6, and IL-1β. A reporter gene assay and EMSA revealed that B-EPS up-regulated the transcriptional activity of NF-κB by increasing its DNA binding and nuclear translocation. Pretreatment with NF-κB inhibitors, that is, BAY11-7082 and PDTC, decreased NO production in IFN-γ-primed RAW 264.7 macrophages by B-EPS. Furthermore, B-EPS increased the proliferation of and cytokine (IL-2 and IFN-γ) production by CD3/CD28-stimulated splenocytes. In a cyclophosphamide-induced immunosuppressed mouse model, B-EPS (5, 15 or 45 mg kg(-1) , p.o.) restored thymus and spleen indices. B-EPS also inhibited cyclophosphamide-induced reductions in neutrophil and lymphocyte numbers. B-EPS improves immune function by regulating immunological parameters in IFN-γ-primed macrophages, CD3/CD28-stimulated splenocytes, and in cyclophosphamide-induced immunosuppressed mice. This study suggests that the exopolysaccharides secreted by B. subtilis J92 could be used as immune stimulants.

Cheonggukjang polysaccharides enhance immune activities and prevent cyclophosphamide-induced immunosuppression

Cheonggukjang is a traditional Korean fermentation product prepared from soybean that is reported to have various biological functions. We previously reported that the polysaccharides from Cheonggukjang (PSCJ) have immunostimulatory activities in RAW 264.7 macrophages and primary cultured splenocytes. In this study, the immunostimulatory activities of the PSCJ were investigated further using various experimental models such as in vitro, ex vivo, and in vivo. The PSCJ was able to stimulate the complement system (ITCH50: 30.6%). In primary cultured mouse peritoneal macrophages, the PSCJ was found to significantly increase nitric oxide and immunostimulatory cytokines (IL-6 and IL-12) production in a concentration-dependent manner (1–100μg/mL). In the normal mice model, the oral administration of the PSCJ increased the weight of spleen (p<0.05 at 100 and 200mg/kg) and improved the phagocytic rates of peritoneal macrophages (p<0.05 at 200mg/kg) and lymphocytes proliferation (p<0.05 at 100 and 200mg/kg). Similarly, the PSCJ markedly restored the decreased lymphocytes proliferation (p<0.01 at 200mg/kg), natural killer cell activity (p<0.01 at 200mg/kg), and white blood cell count (p<0.01 at 100 and 200mg/kg) in the cyclophosphamide-induced immunosuppressed mice model. These results suggest that the PSCJ could be utilized as an effective immunostimulatory agent.

The immunostimulatory and antimicrobial property of two herbal decoctions used in the management of HIV/AIDS in Ghana.

HIV/AIDS is a pandemic retarding economic growth and destroying human capital globally. This study therefore investigated the perceived efficacy of Betula alba (BA) and Sutherlandia frutescens (SF) decoctions used in the management of HIV/AIDS in Ghana. A study on the records of HIV/AIDS patients attending Habibi Herbal Clinic, Kumasi, Ghana, was conducted to obtain information on the initial viral load presented during their maiden visit and results after treatment with the herbal decoctions. The decoctions were assessed for immunostimulatory property in cyclophosphamide-induced immunosuppressed ICR mice. Total white blood cell count, as well as lymphocyte and neutrophil counts were determined and their effects compared with Levamisole. The decoctions were also screened for antimicrobial activity by the micro dilution method. The two herbal decoctions used significantly reduced (P ≤ 0.001) the patients' viral loads (47.42 ± 17.28 % to 13.69 ± 12.42 %; n=16). BA (1, 2, and 4 mg/kg) and SF (0.4, 0.8, and 1.6 mg/kg) caused significant increment (P ≤ 0.001) in total WBC and lymphocyte count in mice comparable to that produced by 2.5 mg/kg Levamisole. The decoctions also exhibited antimicrobial activity against gram negative and gram positive bacteria as well as Candida albicans (MIC 0.607 to 3.062 mg/ml). Phytochemicals present in both plants include saponins, terpenoids and coumarins. The Betula alba and Sutherlandia frutescens decoctions have interesting immunostimulatory and antimicrobial properties and hence could be useful in the management of HIV/AIDS and associated opportunistic infections.

The ameliorative effects of Averroha carambola on humoral response to sheep erythrocytes in non-treated and cyclophosphamide-immunocompromised mice

ObjectiveTo evaluated immunomodulatory and antioxidant activity of the methanol extract of Averrhoa carambola (A. carambola) leaves in mice. MethodsThe assessment of immunomodulatory activity on specific and non-specific immunity was studied by administration of test extract by oral feeding canula to the test groups. Hemagglutinating antibody (HA) titer, delayed type of hypersensitivity (DTH) response, hematological profile (Hb, WBC, RBC), lipid per oxidation (LPO), reduced glutathione (GSH), superoxide dismutase (SOD), catalase (CAT) were determined by in vivo experiments. ResultsThe evaluation of immunomodulatory potential of A. carambola (800 and 1 200 mg/kg, p.o.) evoked a dose-dependent increase in antibody titer values and DTH reaction induced by SRBC was also found significant (P<0.001). Also it caused increase in hematological profile, GSH, SOD, CAT activity and significantly decreased LPO levels in cyclophosphamide-induced immunosuppressed mice. Result shows that the extract treated animals showed up regulation of (IL-6 and TNF-α) cytokines. ConclusionsImmunomodulators are being used as an adjuvant in conditions of immunodeficiency in cancer and to a limited extent in acquired immunodeficiency syndrome. The results obtained in this study indicate that A. carambola possesses potential immunomodulatory and antioxidant activity.

Protective effect of chitooligosaccharides against cyclophosphamide-induced immunosuppression in mice

Chitooligosaccharides (COS) display a variety of important biological activities, including antimicrobial, antitumor, anti-inflammatory, and immunoenhancing. In the present study, a COS sample (degree of polymerization 4–11, analyzed by FTIR and MALDI-TOF-MS) prepared by hydrolysis with a recombinant chitosanase was orally administered to mice for evaluation of its effect on cyclophosphamide (Cy)-induced immunosuppression. Thymus and spleen indices, delayed-type hypersensitivity (DTH) reaction, macrophage phagocytosis, and certain enzyme activities were significantly higher in mice treated with COS+Cy than in mice treated with Cy alone. ELISA experiments showed that COS treatment enhanced production of the cytokines IL-2, IL-12, and IFN-γ but decreased production of IL-10 in sera of Cy-treated mice. The well-defined COS product studied displayed strong immunoenhancing activity and a protective effect against Cy-induced immunosuppression. COS-derived products should be further investigated for possible immunostimulatory applications in the food and pharmaceutical industries.