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Results for “immunomodulation”

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PubMed1988

[Immunomodulators and hemopoietic system in malignant growth].

The data on the effect of immunomodulators (IM) of the biologic origin on hematopoietic responses are reviewed. Up-to-date classification of immunomodulators is given. The correlation between the proliferative stem cell response induced by certain immunomodulators, accidental thymus involution, suppressor T cell activity enhancement and the development of transient anemia are analyzed from the standpoint of its possible significance. A conclusion is drawn on the necessity to develop systemic criteria which permit evaluating shifts induced by immunomodulators in the hematopoietic system.

Adjuvants, Immunologic↗

PubMed1988

Litomosoides carinii in rodents: immunomodulation in potentiating action of diethylcarbamazine.

The antifilarial activity of combination of diethylcarbamazine (DEC) and an immunomodulator, N-Palmitoylmuramyl-L-alanyl-D-isoglutamine (NP-MDP) was evaluated against Litomosoides carinii in cotton rat (Sigmodon hispidus) and Mastomys natalensis. DEC was used at 6 mg/kg in cotton rat whereas it was 75 mg/kg x 5 days in mastomys. The immunomodulator was administered at 62.5 to 500 micrograms/animal x 2 days. Combination therapy with optimum dose of immunomodulator resulted in prolonged and significant suppression of microfilaraemia in comparison to infected animals treated only with DEC. The effective doses of immunomodulator alone or in combination with DEC also caused enhanced antibody titre in treated animals. Though combination therapy resulted in prolonged suppression of microfilaraemia, the effect disappeared slowly and caused no damage to adult worms.

Acetylmuramyl-Alanyl-Isoglutamine↗

PubMed1986

[Changes in the histologic structure of the organs of immunogenesis during treatment with immunomodulators].

The effect of levamisole as well as thymic (thymalin and bone marrow (hemalin) immunomodulators on the immunogenesis organs in practically healthy animals were studied. The comparison of multiple parameters of morphological changes developing in the immunocompetent organs under the influence of immunomodulators was performed by means of so called "similarity ratio". Morphological changes in the central organs of immunogenesis were more severe after the administration of hemalin than after levamisole. The influence of immunomodulators on the peripheral organs of immunogenesis were more uniform. The results obtained in the experiments on healthy animals may serve the basis for a further morphological analysis of the immunomodulators effects under the conditions of the immune homeostasis disturbance.

Adjuvants, Immunologic↗

PubMed1982

Effect of immunomodulation on the fate of tumor cells in the central nervous system and systemic organs of mice. Distribution of [125I]5-Iodo-2'-deoxyuridine-labeled KHT tumor cells after left intracardial injection.

The effect of systemic immunomodulation on tumor cell arrest and retention in the central nervous system was studied by following radioactively labeled tumor cells. KHT mouse sarcoma tumor cells were labeled in vitro with [125I]IdUrd, and 1 X 10(5) tumor cells were injected into the left side of the hearts of syngeneic C3H mice. Experimental groups consisted of untreated normal mice, mice pretreated iv with Corynebacterium parvum, and mice chronically infected with Toxoplasma gondii; in this model both groups of immunomodulated mice are protected from developing systemic metastatic tumor, but only Toxoplasma-infected mice have protection against metastatic brain tumor. At time intervals from 1 to 96 hours, groups of mice from each experimental group were killed, and the brain and other organs were monitored for radioactivity to determine the number of viable tumor cells that had been present at the time of death. Normal mice demonstrated significant retention of tumor cells in the brain and kidneys plus adrenals at 96 hours. By contrast, in both groups of immunomodulated mice tumor cells were rapidly eliminated from systemic organs, but tumor cells were significantly retained in the central nervous system even at 96 hours after tumor cell injections. The results indicated that generalized immunomodulation had more effect in elimination of tumor cells from systemic organs than from the brain and that the elimination of tumor cells from the brain in Toxoplasma-infected mice was a delayed phenomenon.

Animals↗

PubMed1994

[Local immunomodulation in atopic and nonatopic children with nonspecific respiratory tract diseases].

The authors report their own results of local immunomodulation with IRS 19 in 57 atopic and nonatopic children having nonspecific chronical diseases of the respiratory tract. The results were obtained on the basis of complex diagnostical procedures before and after local immunomodulation. These results are demonstrated by tables, figures and graphs. By comparing the results obtained with local immunomodulation, it was found that prophylactic and therapeutic efficiency of IRS 19 is better in nonatopic children than in atopic ones. The detailed analyses showed that the local immunomodulation caused not only an increased concentration of the immunoglobulins IgG, IgM, IgA but also of the IgE.

Adjuvants, Immunologic↗

PubMed1993

[Effect of immunomodulators of organometallic nature on the sensitivity to plague toxin].

Influence of immunomodulators with organometallic origin on sensitivity to mice toxin on CBA, C Bl/6 mice and hybrids F1 (CBA C Bl/6) has been investigated. It has been determined that used immunomodulators are the means of urgent change of sensitivity to plague intoxication (5 min after i.v. administration of immunomodulators, the sensitivity to mice toxin changes). The character of immunomodulators' influence on sensitivity to plague intoxication depends on daily time and animals' genotype.

Adjuvants, Immunologic↗

PubMed1997

Effect of RN-301 immunomodulator on bronchus-associated lymphoid tissue (BALT) in protein depleted rats at weaning.

It has been previously demonstrated in Wistar rats that severe protein deprivation at weaning, even after refeeding with a 20% casein diet for 21 days, provokes alterations in IgA+ B cell and T cell populations from gut and GALT (gut associated lymphoid tissue) that are reverted by immunomodulator IM-104. In the present report, we investigate the influence of RN-301 (quite similar to IM-104) given by the oral or subcutaneous route during the protein deprivation period, in the seeding of BALT with IgA+ B and CD5+ T cells. The immunomodulator RN-301 contains LPS from E. coli and membrane and ribosomal fractions of P. acne. Tissue sections of the lower respiratory tract were studied by immunohistochemistry. The immunomodulator RN-301 administered by the oral route favours the significant increase in the seeding of the BALT lamina propria with IgA+ B and CD5+ T cells (p < 0.001). However, the RN-301 given by the subcutaneous route does not favour the repopulation of the BALT lamina propria. The ribosomal fractions from P. acne associated with LPS from E. coli contained in the immunomodulator RN-301 administered by the oral route may rescue the small resting lymphocytes in the gut-associated lymphoid tissue (GALT). This event favours their proliferation and migration to the BALT.

Adjuvants, Immunologic↗

PubMed1998

Effect of a commercially available nonspecific immunomodulating biologic product on health of neonatal calves.

OBJECTIVE: To determine whether treatment with a commercially available nonspecific immunomodulating biologic product would alter the clinical course of disease in neonatal calves. DESIGN: Systematically randomized, controlled cohort study. ANIMALS: 200 Holstein bull calves 1 to 5 days old. PROCEDURE: Assessments were performed that included evaluation of fecal consistency, attitude, appetite, and hydration status. Calves with abnormal results were enrolled in the study. Calves were systematically assigned to control or treatment groups (100 calves/group). Calves in the treatment group were given a single i.v. injection of the biologic product at the time of enrollment, whereas control calves were not given the product. Calves were assessed daily for 5 days to evaluate fecal consistency, attitude, appetite, hydration status, and rectal temperature. Assessments were made without knowledge of group assignment. RESULTS: Treatment with the immunomodulating product was not associated with a decrease in the number of calves that had moderate or severe departures from clinically normal conditions for attitude, appetite, or hydration on days 1 though 5, compared with control calves. Fecal consistency scores were significantly greater for treated calves on days 1 (P = 0.03) and 5 (P = 0.02), compared with scores for control calves. CLINICAL IMPLICATIONS: Administration of the nonspecific immunomodulating biologic product did not significantly affect outcome of clinical disease for calves in the treated group, compared with calves in the control group. On the basis of results of this study, we cannot recommend use of the nonspecific immunomodulating biologic product for the treatment of undifferentiated diarrheal disease in neonatal calves.

Adjuvants, Immunologic↗

PubMed1991

Surgeons, surgery, and immunomodulation.

With the definition over the past 15 years of the altered immune state of surgical patients as a result of disease itself and surgical therapy, there have been multiple approaches to the modulation of immune status in experimental or clinical situations, but with conflicting or unhelpful results. The variable that has never been assessed is the significance of the surgeon as an immunomodulator. The expediency and the quality of the surgical act in a variety of surgical diseases have a positive effect on the immune system. Indeed, the data indicate that correction of shock, drainage of infection, excision or drainage of necrotic material, restoration of body composition, and solid basic care all have a positive influence on patients' immune responses. An immunomodulator might get credit if the role of surgical care is not properly assessed. A framework for the study of immunomodulators with the integration of clinical behavior is outlined.

General Surgery↗

PubMed1997

Local but no systemic immunomodulation by intraperitoneal treatment of advanced ovarian cancer with autologous T lymphocytes re-targeted by a bi-specific monoclonal antibody.

We have reported a 27% overall anti-tumor response using i.p. immunotherapy of advanced ovarian carcinoma with autologous, ex vivo expanded, T lymphocytes re-targeted with bi-specific monoclonal antibody OC/TR, combined with soluble OC/TR and low-dose recombinant interleukin-2 (IL-2). This treatment had no effect on extraperitoneal disease. Therefore we studied in 13 patients whether this immunotherapeutic protocol resulted only in local or also in systemic immunomodulation. The phenotype of the ex vivo expanded lymphocytes was mainly CD3+, 4-, 8+, 16-, 56-. Their OC/TR-re-targeted cytolytic activity against Igrov-1 ovarian-carcinoma cells was approximately as high in responders as in non-responders. Following most therapeutic cycles, the immunophenotype of lymphocytes recovered from the peritoneal fluid was similar to that of the infused T cells (i.e., mainly CD3+, 4-, 8+) and they were coated with OC/TR. However, cytolytic activity of the recovered lymphocytes against Igrov- 1 cells was low in direct assays, and only slightly increased after additional in vitro re-targeting with OC/TR. Systemically, the i.p. immunotherapy resulted in a transient lymphopenia lasting for about 7 days, low (i.e., 5 to 13 ng/ml) serum concentrations of free, functional OC/TR, and very weak coating of circulating T lymphocytes with OC/TR. These peripheral-blood T lymphocytes did not exert OC/TR-re-targeted cytolytic activity. Thus, locoregional OC/TR-re-targeted cellular immunotherapy resulted in substantial local immunomodulation and anti-tumor effects but virtually no systemic immunomodulation.

Antibodies, Bispecific↗

PubMed1994

Effect of immunomodulators on specific tumor immunity induced by liposome-encapsulated tumor-associated antigens.

Reconstituted membranes consist of liposomal structures formed by removal of detergent from solubilized membrane constituents. The membrane-like configuration of reconstituted membranes makes them attractive as vehicles for presentation of tumor-associated antigens and induction of immune responses. In this study the potential of immunomodulators was assessed to enhance the specific immune response induced by immunization with reconstituted membranes prepared from SL2 lymphosarcoma cells. Reconstituted membranes containing muramyl tripeptide phosphatidylethanolamine (MTP-PE) provided better protection against a challenge with SL2 cells than did reconstituted membranes containing alternative immunomodulators. Local administration of IL-2 at the immunization sites further augmented the protection induced by reconstituted membranes with MTP-PE, but was ineffective when administered with plain reconstituted membranes. Immunity elicited by the triple modality of reconstituted SL2 membranes with MTP-PE and IL-2 was specific for SL2 cells. Systemic immunity was obtained against a challenge with a 100-fold higher number of SL2 cells than was reached after immunization with reconstituted membranes alone (10(5) vs. 10(3) SL2 cells). Macrophages isolated from the peritoneal cavity of immunized mice 5 to 7 days after tumor challenge expressed high in vitro cytotoxicity. However, in contrast to the observed specificity of the systemic immunity, macrophages killed both SL2 cells and non-related P815 cells. Neither major cytotoxic lymphocyte activity nor substantial cytotoxic antibody titers were detectable. These results clearly indicate that the approach using reconstituted membranes combined with particular immunomodulators warrants further exploration for the development of safe, well-characterized cancer vaccines.

Adjuvants, Immunologic↗

PubMed2002

Immunomodulation of experimental colitis via caloric restriction: role of Nk1.1+ T cells.

Inflammatory bowel diseases are immune-mediated disorders. Dietary restriction and NK1.1+ liver-associated lymphocytes (LAL) are considered to be involved in immunomodulation of autoimmune diseases. Our aim was to evaluate the effect of caloric restriction on experimental colitis and to determine NK1.1+ LAL function in immunoregulation. Experimental colitis was induced in C57 black mice by intracolonic instillation of trinitrobenzene sulfonic acid. Caloric restriction to 60% of the daily requirement was started 2 weeks prior to, or simultaneously with, colitis induction and continued throughout the study. Control mice were fed ad libitum. Colitis was assessed by standard clinical and macroscopic scores. To determine the mechanism involved in immunomodulation, liver lymphocytes were isolated and analyzed for NK1.1+ T-cell markers by FACS. T-cell function was evaluated by T-cell proliferation. Serum cytokines were measured by ELISA. Dietary restriction to 60% markedly ameliorated experimental colitis in both groups. These mice gained weight and showed improved macroscopic parameters of colitis. NK1.1+ LAL numbers increased fourfold and NKT cytotoxicity twofold in caloric-restricted mice. The antigen-specific T-cell proliferation index decreased (from 4.45 in controls to 1.15), and IFN-gamma and IL-12 serum levels decreased (from 290 to 200 pg and from 122 to 53 pg, respectively) in caloric-restricted mice. Our conclusion was that dietary restriction induced immunomodulation of experimental colitis and ameliorated the disease. This effect was mediated via an increase in NK1.1+ T lymphocytes, which may play a critical role in keeping the T-cell balance in immunoregulation.

Animals↗

PubMed2002

The effect of dietary immunomodulation upon Edwardsiella tarda vaccination in healthy and immunocompromised Indian major carp (Labeo rohita).

In order to determine the impact on disease resistance of four dietary immunomodulators viz., beta-1,3 glucan, levamisole, vitamins C and E, in an important farmed Indian major carp species, rohu (Labeo rohita Ham.), fish were fed diets containing various levels of these substances during a 60 day trial. Aflatoxin B1 (AFB,) at 125 mg kg(-1) body weight was injected intraperitoneally (i.p.) into fish to induce an immunosuppressive state on the first day of the experiment in some individuals. The fish were vaccinated against formalin-killed Edwardsiella tarda vaccine on day 30 of the experiment. Specific immunity, as measured by bacterial agglutination titre and disease resistance against E. tarda, was determined at the end of the trial. The results demonstrate that all the four immunomodulators were capable of significantly (P<0.05) increasing specific immunity and reducing mortality in immunocompromised fish but failed to enhance specific immunity and protection in healthy fish. The increased bacterial agglutination titre by beta-1,3 glucan, and reduced mortality losses by both beta-1,3 glucan and levamisole were marked in healthy vaccinated fish compared with their controls. Similarly, all four substances significantly reduced the mortality rates in immunocompromised and healthy unvaccinated fish. Out of these four substances, glucan was recorded to be the most effective immunomodulator in rohu. The present results suggest that the introduction of these substances into the diet of fish grown in farms under immunosuppressive/stressful conditions could increase their resistance to infection by reducing mortality rates and offer economic benefits.

Adjuvants, Immunologic↗

PubMed1996

Immunomodulation following chemotherapy.

In the last decade, immunomodulation has emerged as a mode of therapy capable of mediating the regression of cancer in some patients. This article reviews our experience with immunomodulation following transplant and non-transplant chemotherapy. We used interferon and cyclosporine A following conventional chemotherapy in a non-transplant setting for a B16 melanoma in a murine model. This combination generated cells with MHC-unrestricted cytotoxicity. We have also used immunotherapy in the transplant setting with IL-2 activated PBSC in patients with breast cancer. Of the 28 patients treated, 20 developed GVHD and the average time to reconstitution was 12 days (comparable to a control group). This article also raises the possibility of extending immunomodulation to breast cancer patients in the nontransplant setting to induce an antitumor immune response following cytoreductive chemotherapy.

Animals↗

PubMed2002

Immunomodulating and anticoagulant activity of glycosaminoglycans derived from porcine testis.

Glycosaminoglycans (GAGs) were isolated from the porcine testis, and their immunomodulating and anticoagulant activity was investigated. From anion exchange chromatography (Dowex Macropolous Resin) used for further isolation of porcine testis GAGs (PT-GAGs), two fractions (PT-GAG-1.5 and PT-GAG-16) eluted by different salt concentration were obtained. In immunomodulating activity test, PT-GAG-1.5, but not PT-GAG-16, significantly enhanced the growth of murine peritoneal macrophages. In addition, treatment with PT-GAG-1.5 induced the production of cytokines, interleukin-1beta (IL-1beta), interferon-gamma (IFN-gamma) and tumor necrosis factor-alpha (TNF-alpha), from murine microphages. Unexpectedly, both of PT-GAGs had no effect on the growth of murine splenocytes. The anticoagulant activity of PT-GAG-1.5 and PT-GAG-16 was examined by activated partial thromboplastin time (aPTT) assay and thrombin time (TT) assay. Both of PT-kGAGs significantly increased the clotting times of aPTT and TT in a dose-dependent manner. The anticoagulant activity of PT-GAG-16 was found to be higher than that of PT-GAG-1.5. These results suggest that PT-GAGs possess biological activities such as immunomodulating activity and anticoagulant activity.

Adjuvants, Immunologic↗

PubMed1989

Immunomodulation with thymopentin: in vitro studies.

Immunomodulation is interpreted as a temporary alert in a certain part of the immune system. The activation of immune competent cells is presented as a possible basic mechanism of this phenomenon. In the absence of a primary stimulus, immunomodulation remains physiologically silent, but it results in a modified immune response if the corresponding targets are being stimulated. For practical reasons it is suggested that distinctions be made between preventive and regulative immunomodulation. The PWM-induced IgG production of PBMCs was used as a model for the demonstration of the modulatory effect of thymopentin in vitro. Depending on the concentration of thymopentin used in the cultures, this pentapeptide can either stimulate or inhibit the induced IgG production. It also influences PGE2 production and catabolism in the cultures stimulated with PWM. Indomethacin abolishes the modulatory effect of thymopentin on IgG production in this model. It is suggested that the possibility of interactions between an immune modulator and therapeutic approaches which can influence the proportions or functions of the corresponding target cells be considered.

Adjuvants, Immunologic↗

PubMed2002

Effect of mucosal immunomodulation with fed cholera toxin on healing of experimental colonic anastomosis.

PURPOSE: The aim of this study was to investigate in rats whether preoperative orogastric administration of low doses of cholera toxin would influence the mechanical strength of experimental colonic anastomosis on the basis of the gut mucosal immunomodulation effect of this antigen. METHODS: The cholera toxin group (n = 14) was fed 10 microg of cholera toxin in phosphate-buffered saline three times before surgery at 10-day intervals, whereas the controls (n = 14) received phosphate-buffered saline only. Twenty-four hours after the last dose of cholera toxin (or placebo in control group), the animals underwent left colonic transection and anastomosis. Seven days after colonic transection-anastomosis, the bursting pressure of the anastomotic segment was recorded in situ. Perianastomotic and extra-anastomotic tissue samples were obtained for measurements of tissue transforming growth factor-beta, interleukin-6, and interferon-gamma levels with enzyme-linked immunosorbent assay. RESULTS: Cholera toxin administration resulted in a significantly higher bursting pressure than in the control group (165.78 +/- 12.37 vs. 138.4 +/- 7.87 mmHg; P < 0.001). Compared with the control group, the heightened mechanical strength of colonic anastomosis provided by cholera toxin was associated with significant increases in the perianastomotic tissue levels of transforming growth factor-beta (199.34 +/- 24.85 vs. 70.66 +/- 10.63 pg/ml; P < 0.001) and interleukin-6 (439.31 +/- 95.14 vs. 289.57 +/- 96.59 pg/ml; P = 0.001), whereas interferon-gamma was significantly lower (174.04 +/- 44.82 vs. 219.00 +/- 31.35 pg/ml; P < 0.05). This cytokine pattern induced by cholera toxin in the wound milieu was also found to be similar in the extra-anastomotic colon. CONCLUSION: The mechanical strength of uncomplicated experimental colonic anastomosis increased significantly with gut mucosal immunomodulation with repeated low preoperative doses of cholera toxin. This enhanced healing had significant positive correlation with the colonic tissue level of transforming growth factor-beta and inverse correlation with interferon-gamma. If the relevant dose regimen is identified and its safety is assured in humans, gut mucosal immunomodulation might provide an efficient, safe, and inexpensive tool to improve surgical outcome in colorectal surgery, particularly in high-risk situations.

Adjuvants, Immunologic↗

PubMed1994

Chemotherapy of experimental filariasis: enhancement of activity profile of ivermectin with immunomodulators.

The effect of certain immunopotentiators (Freund's complete adjuvant, picroliv, tuftsin and CDRI Compound 86/448) was evaluated on exertion of antifilarial activity of ivermectin at different dose levels in cotton rats experimentally infected with Litomosoides carinii. Ivermectin alone (up to 250 micrograms/kg p.o. x 5 days) caused sterilization of most of the surviving female parasites, but had no lethal effect on adult worms. In combination with immunomodulators, ivermectin brought about significant lethal effect on adult parasites even at a dose of 1 microgram/kg x 5 days. Nevertheless, in animals receiving FCA alone, sterility was caused in > 50% of female parasites. Other immunomodulators used alone had a suppressive effect on microfilaraemia only. Immunomodulators alone or in combination with ivermectin also caused enhanced filaria-specific antibody response.

Adjuvants, Immunologic↗