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Results for “immunomodulation”

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PubMed1998

Papillomavirus-induced genital warts in a girl--management by surgery and immunomodulating therapy.

A 4-year-old girl with condylomata acuminata of the vulva and papular warts of the surrounding skin is presented. The lesions were removed by surgery. Histologic investigation showed koilocytosis of the squamous epithelium and in-situ hybridization revealed human papilloma virus type 6 infection. There were no signs of sexual abuse or sexual transmission of the virus. After ablation, an interferon-containing ointment was applied. In order to prevent recurrence, a low-molecular-weight immunomodulating leucocyte fraction was given for more than 1 year, during which time no relapse was observed.

Adjuvants, Immunologic↗

PubMed2004

Experimental infection of immunomodulated NOD/LtSz-SCID mice as a new model for Plasmodium falciparum erythrocytic stages.

The main objective of this study was to determine whether a chemical immunomodulation protocol could reduce the resistance of NOD/LtSz-SCID mice to Plasmodium falciparum infection and provide an improved mouse model for screening the antimalarial activity of new compounds. This model was compared with the presently used immunodeficient Beige/Nude/Xid (BNX) mouse model, using the same protocol, in terms of percentage of infected mice, parasite development, leukocyte response and phagocytosis of P. falciparum infected cells in various organs. Our results show that the combination of the chemical immune modulation protocol with the genetic background of NOD/LtSz-SCID mice results in the development of long-lasting P. falciparum infection in a high percentage of mice. A comparison of the results obtained in the histological study for both mouse models suggests that the higher rate of success in NOD/LtSz-SCID mice could be related to the reduced macrophage recruitment developed in different tissues to remove the parasite from blood.

Animals↗

PubMed2001

Treatment with benznidazole and its immunomodulating effects on Trypanosoma cruzi-infected rats.

Because benznidazole (BZL) was found to downregulate nitric oxide (NO) and cytokine synthesis by murine macrophages, we analyzed the potential immunological repercussions of BZL treatment in Trypanosoma cruzi-infected rats. To evaluate whether the effects of BZL were also observed in the presence of an immunostimulating cytokine, four groups of acutely infected rats were subjected to one of the following 20-day therapeutic schedules: (1) a curative BZL oral regimen, (2) recombinant interferon (IFN-gamma) injections, (3) a suboptimal BZL regimen (25% of curative dose), (4) the latter plus IFN-gamma. All BZL doses markedly reduced NO-derived metabolites either in the circulation or in cultured macrophage supernatants. This was observed in rats simultaneously treated with IFN-gamma, which contrasted with the augmented NO production seen in animals given this cytokine alone. The untreated rats, and groups receiving monotherapy with IFN-gamma or 25% BZL, had increased circulating interleukin (IL)-1beta and IL-2 levels, which were reduced in those given BZL plus IFN-gamma. Although combined treatment failed to cause the virtually undetectable blood parasite levels induced by optimal BZL doses, chronic myocardial lesions were reduced to the same extent as in those receiving the curative schedule. The beneficial effects of BZL in this trypanosomiasis may also depend on some immunomodulating influences.

Adjuvants, Immunologic↗

PubMed2002

Increased rates of pulmonary metastases following sham laparotomy compared to CO2 pneumoperitoneum and the inhibition of metastases utilizing perioperative immunomodulation and a tumor vaccine.

BACKGROUND: Subcutaneous tumor growth and establishment is increased after laparotomy; significantly smaller increases have been noted after CO2pneumoperitoneum (CO2 pneumo). Less is known about the impact of surgery on the fate of blood borne tumor cells. The extent of surgical abdominal wall trauma also correlates with the extent of early postoperative immunosuppression and the inflammatory response. These changes may favor lung metastases (mets) formation. This study's hypotheses were: (a) a reduction in surgical trauma or (b) a perioperative (periop) tumor vaccine or nonspecific immune up-regulation would limit lung mets formation. An intravenous tumor cell injection lung met model was used to test these hypotheses. METHODS: Study 1 determined the incidence of lung mets after sham laparotomy (OP) and CO2 pneumo. Three groups were studied (n=25/group) : Anesthesia control (AC), CO2 pneumo, and OP. 1 x 105 TA3Haushka adenocarcinoma cells were inoculated via tail vein injection into all mice immediately after surgery. Study 2 determined the impact of perioperative immunomodulation on lung mets formation. Five groups were studied (n=20/group) : AC, OP, OP + Monophosphoryl Lipid A (MPLA), OP + lysed tumor cells (LTC), or OP + MPLA + LTC. The vaccine consisted of 5 x 105 lysed TA3Ha tumor cells (LTC) and was given 5 times preop and once postop to the vaccine groups. MPLA, the nontoxic moiety of lipopolysaccharide, was used both as a vaccine adjuvant in the OP + MPLA + LTC group and as a nonspecific perioperative immune up-regulator in the OP + MPLA group. Five periop injections of MPLA were given to the OP + MPLA group. All mice were given tail vein injections of tumor cells after surgery. Fourteen days after surgery all mice were sacrificed, the lungs transected en bloc, and India ink injected into the trachea. The lungs were placed in Fekete's solution to counterstain the tumor foci white. The number of surface lung metastases was determined by two blinded observers, separately. RESULTS: In Study 1, there were significantly more lung tumors in the OP group (median=31.5) than the AC group (median=9; p<0.05) or the CO2 Pneumo group (median=6.5; p<0.05). There were no significant differences in the number of metastases between the AC and the CO2 Pneumo groups or in the incidence of animals in each group with 1 or more lung mets. In Study 2 significantly fewer metastases were noted for the Op + LTC group (median=3; p<0.05) and the OP + LTC + MPLA group (median=0; p<0.05) when compared to the OP group (median=20). Although the OP + MPLA group mice had fewer metastases (median=4) than the OP group, this difference was not significant. Significantly fewer of the OP + LTC + MPLA group mice developed one or more lung tumors than in the OP, OP + MPLA, and the OP + LTC groups. CONCLUSIONS: Full sham laparotomy was associated with more postoperative lung metastases than CO2 pneumo or anesthesia alone in this murine model. Up-regulation of the immune system in the perioperative period with lysed tumor cells, alone or in combination with MPLA, resulted in significantly fewer postoperative lung metastases. MPLA alone resulted in a less marked reduction of lung metastases.

Adenocarcinoma↗

PubMed2005

A post-marketing study on immunomodulating treatments for relapsing-remitting multiple sclerosis in Lombardia: preliminary results.

The preliminary results of a post-marketing study on relapsing-remitting multiple sclerosis patients treated with immunomodulating agents attending the Lombardia Region's Multiple Sclerosis Centers are presented. A total of 294 patients treated with Betaferon (67), Avonex (115), Rebif 22 (45), Rebif 44 (18) and Copaxone (49) were included. Relapse frequency consistently decreases at 1 year and continues to decrease after 5 years of treatment, without differences between therapeutic groups. Eighty-seven out of 294 patients (29.6%) discontinued treatment for different reasons. Forty-eight of them shifted to a second therapeutic agent. A different trend, to lower or higher doses of interferon or immunosuppression, according to reasons of discontinuation, was observed.

Adjuvants, Immunologic↗

PubMed2003

[Topical immunomodulators for treatment of eczema].

Anti-inflammatory treatment of eczematous skin diseases like atopic dermatitis and allergic contact dermatitis has mainly been performed with topical glucocorticosteroids. Increasing knowledge of the pathophysiological interactions and the immunological mechanisms during the chronic inflammatory processes in the skin offers new therapeutical options. In this review, new therapeutical approaches for the treatment of eczematous skin disease will be presented. These novel compounds include the topical immunomodulators, tacrolimus and pimecrolimus. Such molecules inhibit intracellular signal transducing phosphatases and act consecutively at the molecular level by inhibiting the activation of transcription factors. Secondly, the development of nuclear hormone receptor family members, such as retinoids, vitamin D and peroxisome proliferator-activated receptor agonists, is discussed. Substances from this family have differentiating, antiproliferative, but also immuno-modulatory effects, which make them attractive as anti-eczematous therapeutic compounds. The diversity of these interactions is extensive, and clinical studies will prove their clinical efficacy.

Adjuvants, Immunologic↗

PubMed2004

A peptide based on the complementarity determining region 1 of a human monoclonal autoantibody ameliorates spontaneous and induced lupus manifestations in correlation with cytokine immunomodulation.

A peptide based on the sequence of the complementarity determining region (CDR) 1 of a human monoclonal anti-DNA autoantibody that bears the 16/6 idiotype (16/6Id) was synthesized as a potential candidate for the treatment of SLE patients. The peptide, designated hCDR1, did not induce experimental SLE upon active immunization of mice. The ability of the peptide to treat an already established lupus that was either induced in BALB/c mice or developed spontaneously in (NZB x NZW)F1 mice was tested. Ten weekly injections of hCDR1 (200, 50 microg/mouse) given subcutaneously mitigated disease manifestations (e.g., leukopenia, proteinuria and kidney damage) and resulted in a prominent reduction in the dsDNA specific antibody titers. Furthermore, treatment with hCDR1 resulted in reduced secretion and expression of the "pathogenic" cytokines [i.e., INFgamma, IL-1beta, TNFalpha (in the induced model) and IL-10], whereas the immunosuppressive cytokine TGFbeta was up-regulated. Thus, the significant ameliorating effects of hCDR1 are manifested at least partially via the immunomodulation of the cytokine profile. These results suggest that hCDR1 is a potential candidate for a novel treatment of SLE patients.

Animals↗

PubMed2005

Immunomodulation of cucumber mosaic virus infection by intrabodies selected in vitro from a stable single-framework phage display library.

Immunomodulation by the ectopic expression of intracellular antibodies ('intrabodies') has a great potential for interfering with physiological or pathological functions in vivo in a highly specific manner. One of the major obstacles of this technology is the inability of most antibodies to properly fold and function in the reducing environment of the cytoplasm, which prevents the formation of essential disulfide bonds. We wished to assess the intracellular performance of antibodies derived from a semi-synthetic single-chain variable fragment (scFv) phage display library ('F8 library') built on a thermodynamically stable single-framework scaffold. To this purpose, we chose to modulate the infection of a pandemic plant pathogen, the cucumber mosaic virus (CMV). After in vitro 'biopanning' on immobilized virions, two scFvs were biochemically characterized, showing high affinity toward the antigen. They were transiently expressed at high yields as soluble molecules in the cytoplasm of Nicotiana benthamiana plants. Subsequently, they were expressed in the cytoplasm of transgenic tomato plants. Challenge with high viral dose showed that both scFvs were able to elicit a phenotypic effect and led to the identification of a transgenic line fully resistant to infection. In these plants, the scFv binds the virus in the inoculated leaves preventing viral long distance movement. This work represents the first demonstration that the 'F8 library' can be directly screened in vitro to rapidly isolate antigen-specific scFvs that act as effective intrabodies in vivo. These antibodies represent powerful tools to interfere with several intracellular targets, modulating pathogen infectivity and/or cellular metabolism.

Antibodies, Monoclonal↗

PubMed1985

Human placenta-eluted gammaglobulins in immunomodulating treatment of rheumatoid arthritis.

Thirty-one patients with severe rheumatoid arthritis were treated with intravenous perfusion of human placenta-eluted gammaglobulins. These gammaglobulins, which are IgG eluted from placental tissue, have strong immunomodulating properties in vitro. Several clinical trials were tested to find the optimal useful dosage. A 50 percent improvement was considered a good result and was obtained in 60 percent of patients with rheumatoid arthritis. The best results were obtained in patients receiving 1,500 mg daily seven days each month. Six subjects had a long remission of their disease after the end of treatment. The side effects were usually minor. In all patients, an immunostimulation of lymphocyte function was shown, even when they had no improvement. A control group of patients underwent perfusion with IgG from placental blood without any clinical or immunologic effect. It is suggested that the in vivo effects of placenta-eluted gammaglobulins might be mediated by polyspecific anti-HLA-DR antibodies.

Adult↗

PubMed1989

Stimulation of 12-HETE production in human platelets by an immunomodulator, LF 1695. Evidence for activation of arachidonate liberation coupled to cyclo-oxygenase inhibition.

Upon incubation with human platelets previously labelled with [14C]arachidonic acid, a new immunomodulator, LF 1695, induced the accumulation of [14C]-12-(S)-hydroxy-5,8,10,14-eicosatetraenoic acid (12-HETE). Although the time course of [14C]HETE accumulation was identical with 60 microM LF 1695 and calcium ionophore A23187, the latter compound also promoted the formation of 14C-labelled thromboxane B2 and 12-(S)-hydroxy-5,8,10-heptadecatrienoic acid (HHT), whereas 12-HETE was the only arachidonic acid metabolite generated under the action of LF 1695, suggesting that the drug inhibited cyclo-oxygenase. This was further confirmed by the fact that LF 1695 inhibited the second wave of platelet aggregation induced by ADP as well as arachidonic acid effects. Cell lipid analysis revealed that arachidonic acid was liberated from both triacylglycerol and phosphatidylcholine. The effect was observed in the concentration range 15-90 microM, with a half-maximal effect at 30 microM for HETE production, 15 microM for triacylglycerol hydrolysis and 45 microM for phosphatidylcholine deacylation. Incubation of platelets with [14C]arachidonic acid in the presence of 60 microM LF 1695 resulted in a strong inhibition of arachidonic acid incorporation into the various cell lipids, indicating that arachidonic acid mobilization might be due to inhibition of reacylation processes. It is concluded that LF 1695 displays an original and complex effect on platelet lipid metabolism, resulting in the specific generation of lipoxygenase metabolites.

12-Hydroxy-5,8,10,14-eicosatetraenoic Acid↗

PubMed1992

The structure of mytilan, a bioglycan-immunomodulator isolated from the mussel Crenomytilus grayanus.

Mytilan, isolated from the mantle of the mussel Crenomytilus grayanus and which possesses high immunomodulating activity, is a non-covalently linked complex of a polysaccharide (95%) and protein (5%) with lectin activities. Chromatography of mytilan on agarose separated the polysaccharide and protein constituents. The protein appeared to have the lectin properties. Methylation analysis, Smith degradation, digestion with alpha-amylase, and 13C-n.m.r. spectroscopy showed the polysaccharide to be a glycogen-like alpha-D-glucan.

Adjuvants, Immunologic↗

PubMed1983

Polyclonal antibody-forming cell activation and immunomodulation of the in vitro immune response induced by streptococcal extracellular products.

The capacity of three different extracellular streptococcal products to induce polyclonal activation of precursors of plaque-forming cells (PFC) was investigated. The gamma fraction (pI = 4.2), previously shown to be only weakly mitogenic, was the most potent activator of rabbit and mouse immunoglobulin-secreting cells. The polyclonal stimulation induced by the two other fractions (kappa: pI = 4.8 and epsilon: pI = 10.3), shown to be mitogenic in both systems, was only observed in the rabbit system. Using these fractions, the in vitro immunomodulation of the anti-sheep red blood cell immune response was also investigated. Both gamma and epsilon fractions were shown to possess adjuvant properties, whereas the kappa fraction was a suppressor of the specific immune response. It appears, therefore, that the diversified immunological activities observed with extracellular streptococcal products can be dissociated and belong to different entities.

Animals↗

PubMed1984

Immunomodulating properties of two synthetic adjuvants: dependence upon type of antigen, dose, and time of administration.

The effects of two synthetic adjuvants on the antibody response to sheep red blood cells (SRBC) as a thymus dependent (TD) antigen and to dinitrophenyl59-Ficoll as a thymus-independent (TI-1) antigen were investigated in mice. Both dimethyldioctadecylammonium bromide (DDA) and dextran sulfate (DXS) augmented the humoral response to SRBC but not to dinitrophenyl59-Ficoll if injected simultaneously with antigen. Dose-response curves of both antigen and adjuvant revealed that DXS compared to DDA is a more effective adjuvant for the induction of a humoral response to SRBC. Intraperitoneal injection of DDA or DXS evoked a sequence of distinct immune responsive states in mice, measured by the capacity to develop an anti-SRBC response. A short immune-potentiating period (less than 6 hr) is followed by a suppressive, second immune-potentiating state. The immune suppressive state lasted for a period of about 8 days and was restricted to TD-antigens. Suppression could be totally overridden by injection of DDA or DXS simultaneously with antigen, suggesting that the suppressive state was reversible. The kinetics of the observed alteration of the immune response by DDA and DXS were very similar. It is concluded that differences in the modulation of the immune response by DDA and DXS are limited to the initial state. Long-term effects like the induction of a succession of distinct immune responsive states, are more or less similar for both adjuvants. Possible mechanisms by which these immunomodulators interfere with the immune system are discussed.

Adjuvants, Immunologic↗

PubMed1988

Differential immunomodulation by anti-CD2 monoclonal antibodies of anti-CD3-induced T cell activation: dependence upon the individual anti-CD3 monoclonal antibody used for activation.

Two monoclonal antibodies (mAb) recognizing different CD2 epitopes each inhibited anti-CD3-induced proliferation and anti-CD3-induced increase in surface CD2 expression. The magnitude of inhibition by either anti-CD2 mAb was dependent upon which anti-CD3 mAb was used as the stimulus, being more pronounced when the anti-CD3 mAb 454 was used as the stimulus than when either anti-CD3 mAb 147 or 446 was the stimulus. The effects of neuraminidase-treated sheep erythrocytes (which bind to CD2) were also more pronounced on mAb 454-induced proliferation than on mAb 147- or 446-induced proliferation. Furthermore, the effects of preincubation with anti-CD2 mAb depended upon the responder status of the donor to IgG1 anti-CD3 mAb. Preincubation of high-responder cells with anti-CD2 mAb had little effect on subsequent IgG1 anti-CD3-induced proliferation. In contrast, preincubation of low-responder cells with anti-CD2 mAb usually augmented the otherwise small proliferative response to IgG1 anti-CD3 mAb. Taken together, these observations suggest that interaction of surface CD2 with ligand alters the response of T cells to anti-CD3 mAb, but these effects depend upon the individual anti-CD3 mAb used for stimulation. These studies raise the possibility that perturbation of different parts of the CD3-T cell antigen receptor complex may lead to different sequelae, and, as a result, the T cell may respond to a given immunomodulator in different ways.

Antibodies, Monoclonal↗

PubMed1992

In vivo synergistic effect of the immunomodulator AS101 and the PKC inducer bryostatin.

The immunomodulator AS101 has recently been found to have radioprotective properties when injected prior to sublethal and lethal doses of irradiation. In addition, this compound was found to protect mice from hemopoietic damage caused by sublethal doses of cyclophosphamide (CYP) and to increase the rate of survival of mice treated with lethal doses of CYP. AS101 was previously shown to exert a synergistic effect with the PKC-inducer bryostatin in cytokine secretion in vitro. The present studies were designed to evaluate the effects of in vivo combined treatment with AS101 and bryostatin on bone marrow and spleen cellularity and on the number of committed progenitors in the bone marrow at various points of time after their treatment with a sublethal dose of CYP or irradiation. In addition, the combined effect was tested on the survival of mice irradiated with a lethal dose of irradiation. Our data show the presence of synergism which greatly enhances the number of bone marrow and spleen cells 48 hr and 9 days after CYP treatment or irradiation. The combined effect was also demonstrated when bone marrow colony-forming units granulocyte-macrophage (CFU-GM) progenitor cells were evaluated. Moreover, AS101 and bryostatin synergized in their protective effects against lethal damages of irradiation. These results strongly suggest that bryostatin, which lacks tumor-promoting activity, is a particularly good candidate in combination with AS101 for treatment in vivo in counteracting chemotherapy- or radiation-induced hematopoietic suppression or in generally improving the restoration of immune response under conditions involving immune or hemopoietic damage.

Adjuvants, Immunologic↗

PubMed1988

Morphine-induced immunomodulation is not related to serum morphine concentrations.

Morphine pellets produced atrophy of the spleen and thymus and affected mitogen-induced lymphocyte proliferation in mice as characterized by marked suppression of concanavalin A-induced blastogenesis at 48 h, and mild stimulation at 120 h. Morphine blood levels in these animals indicated that changes in the immunomodulatory effects of morphine over time were not related to dramatic shifts in circulating morphine. Enclosure of the pellet in nylon mesh did not alter blood levels or morphine-induced immunomodulation.

Animals↗

PubMed1984

The immunomodulating effect of TP5 and indomethacin in burn-induced hypoimmunity.

Hypoimmunity after major trauma and thermal injury appears to predispose to septicemia. An increase of immune suppressive T cells and the inhibitory monocytes product PGE2 has been demonstrated postburn and are suggested as contributing to postburn hypoimmunity. TP5, the biologically active part of thymopoientin, has an immunomodulating effect on T cells. Indomethacin, an irreversible blocker of the prostaglandin synthesis has been suggested to reduce the inhibitory monocytes-mediated immunosuppression. In this study strains 2 and 13 guinea pigs received 20-30% TBSA scald burn and were subsequently injected with either TP5 or indomethacin or a combination of both on the 3 following days postburn. The ability of splenocytes to produce a secondary immune response to SRBC was measured in the in vitro AFC assay. The animals who had received TP5 and indomethacin showed significant improvement in their ability to mount an immune response in the AFC assay.

Animals↗

PubMed1994

Immunomodulation by morphine in Plasmodium berghei-infected mice.

The effect of morphine on immunomodulation and host defense have been investigated during Plasmodium berghei infection in BALB/c mice. A single low (5.0 mg/kg) subcutaneous dose of morphine strongly suppressed (sometimes completely eliminated) the parasitaemia, whereas a high dose (80.0 mg/kg) exerted mild potentiating effect. Mice treated with the low dose showed a significant (p < 0.05) increase in the total number of circulating leukocytes, the number (pool-size) of peritoneal macrophages, and the phagocytic activity of peritoneal macrophages, in vitro. Conversely, in mice treated with the high dose, all these parameters were diminished. Silica (3.0 mg/mouse), administered intravenously, abrogated the morphine-induced protective effects but did not affect its potentiation of the infection. Naloxone pretreatment (4.0 mg/kg) completely blocked the protective effects of morphine, suggesting the mediation via naloxone-sensitive opiate-receptors; paradoxically, it did not affect the potentiating effects. These observations indicate that morphine exerted a dose-dependent, biphasic effect on the course of P. berghei infection in mice, apparently by modulating the macrophage-mediated protective mechanisms.

Adjuvants, Immunologic↗