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At least 19 recordsLinked to original sources
PubMed1989

[Clinical evaluation of immunosuppressive factors (IAP-immunosuppressive acidic protein, IS-immunosuppressive substance) in head and neck cancer].

It is reported that the levels of serum IAP and IS are useful parameters to evaluate the prognosis along with the clinical course of tumor bearing patients. Serum IAP and IS were examined in 149 patients with head and neck cancer. The level of serum IAP and IS increased in patients with not only advanced stages, but also poor prognosis. In general, the patients with death or recurrence had higher levels of serum IAP and IS than those with good prognosis. It is concluded that serum IAP and IS well reflect the immunological condition and clinical course of patients with cancer and may be one of the useful parameter for them.

Adolescent↗
PubMed1991

[Screening of active anti-inflammatory, immunosuppressive and antifertility components of Tripterygium wilfordii. III. A comparison of the antiinflammatory and immunosuppressive activities of 7 diterpene lactone epoxide compounds in vivo].

The half-effective dose(ED50), therapeutic index(TI) and certain safety factor(CSF) of 7 diterpene lactone epoxide compounds with antiinflammatory and immunosuppressive action extracted from Tripterygium wilfordii (TW) were assayed using croton oil-induced ear swelling and hemolysin-antibody formation mouse models. The results indicated that triptolide(T10), tripchlorolide(T4), triptonide(T7), tripdiolide(T8), triptolidenol(T9) and 16-hydroxytriptolide(L2) possessed both anti-inflammatory and immunosuppressive activities, while triptriolide(T11) had antiinflammatory activity only. The TI of the antiinflammatory action of 7 compounds were arranged in following order: T11(greater than 19), T10(17), T9(9.6), T4(9.0), T8(7.3), L2(6.6), T7(5.9), while the TI of the immunosuppressive action of 6 compounds were arranged in following order: T9(30.7), T4(16.7), L2(15.8), T10(13.7), T8(8.8), T7(7.5). The CSF parameters of both the activities of 7 compounds were all higher than 1. In which, the CSF of the immunosuppressive action of T9, T4 and L2 were 7.1, 5.1 and 3.6 respectively. These facts clearly demonstrate that the antiinflammatory and immunosuppressive compounds in TW are pluralistic. These differences among these compounds can be used as one of the bases for the evaluation and selection of these compounds. The above experiments conclude that the practical value of these compounds, however, will also depend on their content and yield rate in the herb, on the degree of difficulty in synthesizing these compounds, and on difficulty involved in the preparation of their derivatives. The future of these compounds will depend on the results of genetic toxicology studies as well.

Animals↗
PubMed1992

The impact of triple drug immunosuppression on clinical results of cadaveric kidney transplantation: a comparison of conventional immunosuppression.

A retrospective study was carried out in 110 cadaveric kidney transplant recipients to compare the effects of low doses of cyclosporine (CsA), azathioprine (AZP) and steroids (triple-drug therapy) with those of higher doses of steroids plus AZP (conventional immunosuppression). Graft survival rate in the triple-drug therapy was 77%, 69%, and 69% at 1, 3, and 5 years, respectively. This was significantly better than 48%, 34%, and 29% in conventional immunosuppression. The incidence of acute rejection episodes was significantly lower in the triple-drug therapy than in conventional immunosuppression (25% vs 58%). In conclusion, our study shows that triple-drug therapy using low-dose cyclosporine is the safest of the immunosuppressive regimens and provides a beneficial effect on the long-term survival of cadaveric kidney transplants.

Adult↗
PubMed1976

Influence of immunosuppression on the action of antimycobacterial drugs in experimental tuberculosis. I. Effects of isoniazid, rifampicin and streptomycin on the survival of tuberculous mice immunosuppressed by azathioprine (Imuran).

The influence of the host immunosuppression on antimycobacterial effects of isoniazid, rifampicin or streptomycin was studied on animal models. Differences in survival rates of mice influenced or uninfluenced by azathioprine (Imuran) and exposed to six applications of antituberculous drugs (given once a day in the monotherapy) were statistically evaluated. The dose-dependent antimycobacterial effects of rifampicin or isoniazid were not significantly altered by the immunosuppression of the host. In contrary to that definite dose-dependent effect of streptomycin, observed in azathioprine-uninfluenced mice, cannot be confirmed in immunosuppressed mice in which no effect of streptomycin on the survival of tuberculous mice could be estimated.

Animals↗
PubMed1991

Dunaimycins, a new complex of spiroketal 24-membered macrolides with immunosuppressive activity. III. Immunosuppressive activities of dunaimycins.

The immunosuppressive effects of the dunaimycins, a new complex of spiroketal 24-membered macrolides, were compared to cyclosporin A, ascomycin, and rapamycin. Each dunaimycin was a potent inhibitor of the mitogenic response observed in mixed murine splenocyte or human leukocyte cultures, and like immunosuppressive drugs these compounds were relatively less potent inhibitors of the constitutive proliferation of murine EL4 thymoma cells. Dunaimycin D4S showed no selectivity in inhibiting the mitogenic response of spleen cells to concanavalin A, pokeweed mitogen, lipopolysaccharide, or phytohemagglutinin. Cyclosporin A and ascomycin did not inhibit interleukin 2 dependent proliferation, whereas the dunaimycins and rapamycin blocked the uptake of [3H]thymidine in mixed cultures supplemented with exogenous interleukin 2. In addition, dunaimycin D4S had no apparent affinity for cyclosporin A or FK-506 immunophilins. Although the dunaimycins inhibited the activity of Na+, K(+)-ATPase, inhibition of this enzyme appeared insufficient to explain the biological activity of these new macrolides. Over a narrow concentration range, dunaimycin D4S showed in vivo immunosuppressive activity in the murine popliteal lymph node hyperplasia model.

Animals↗
PubMed1991

Renal allograft immunosuppression. VI. Triple drug therapy versus immunosuppressive double drug combinations: histopathological findings in renal allografts.

The long-term effects of different immunosuppressive drugs and regimens on renal allograft histology are virtually unknown. Therefore, in order to investigate the long-term effects of triple drug treatment versus different combinations of two immunosuppressive drugs on allograft histology, a prospective, randomized trial was performed. One group received triple therapy consisting of low-dose cyclosporin (CyA), azathioprine (Aza), and methylprednisolone (MP), and three groups received combinations of two drugs, i.e., Aza plus CyA, Aza plus MP, and CyA plus MP. At 2 years, there were no significant differences with regard to graft (80%) or patient (87%) survival, or to graft function between the four groups. After 2 years, a protocol core biopsy was taken of all 102 patients having a functioning graft. Of these patients, 61 (60%) were still following the original, randomized treatment protocol; in the remaining cases, changes had occurred in the original protocol and so these cases were considered drop-outs in this study. Histological specimens were examined blindly by two independent observers. Most of the 34 histological variables examined showed no changes. Diffuse fibrosis was most frequent in the CyA plus MP group (70%) and significantly more severe than in the triple therapy group. Mesangial matrix increase in glomeruli was significantly less common in the triple therapy group (8%) than in any one of the double drug combination groups (47%). Two other changes in glomeruli--Bowman capsular thickening and global glomerular sclerosis--were also less frequent in the triple therapy group.(ABSTRACT TRUNCATED AT 250 WORDS)

Drug Therapy, Combination↗
PubMed1989

Effects of CKS-17, a synthetic retroviral envelope peptide, on cell-mediated immunity in vivo: immunosuppression, immunogenicity, and relation to immunosuppressive tumor products.

CKS-17 is a heptadecapeptide corresponding to a region highly conserved in retroviral transmembrane proteins such as p15E. Because a relationship had previously been determined between p15E and immunosuppressive tumor cell products, we examined the effect of CKS-17, control peptides and conjugates thereof on the expression of cell-mediated immunity (delayed-type hypersensitivity, DTH) in mice. Conjugates of CKS-17 inhibited DTH reactions to sheep erythrocytes in the feet of mice. The degree of inhibition was dose-dependent. Unconjugated CKS-17 had almost no effect, and control peptide conjugates had no inhibitory effect. Immunization of mice with CKS-17 conjugates, but not with control conjugates, rendered them resistant to the depression of DTH reactions, not only by CKS-17 conjugates, but also by products of cultured tumor cells. CKS-17 conjugates, but not control conjugates, also depressed the cellular inflammatory reactions induced in mouse footpads by concanavalin A (ConA) and immunized mice against the depression of ConA reactions by products of cultured tumor cells. Injections of globulin from sera of mice immunized with CKS-17 conjugates conferred upon normal recipients resistance to the depression of footpad reactions to ConA by products of cultured tumor cells. Globulin from sera of normal mice or control immunized mice did not confer such resistance. Thus conjugates of a synthetic peptide not only mimic the immunosuppressive effects of tumor products in vivo, but can also immunize mice against those effects.

Animals↗
PubMed1976

[Modification of the immune reaction by antigen-immunosuppressive-agent conjugates. I. Tentative hypothesis for the induction of antigen-specific suppression by antigen-immunosuppressive-agent conjugates].

The most important mechanisms for the specific depression of immune reactions--immuno-tolerance, enhancement, transfer of antibodies, drug induced tolerance, immunological suicide, application of antibody-toxin-complexes--are discussed with regard to their possible application in the clinical practice. A tentative hypothesis for induction of antigen specific suppression is proposed, basing on the use of antigen-immunosuppressive agent-conjugates (AIC). Antigen binding lymphocytes are supposed to bind the AIC and to pick them up through endocytosis. After breakdown of the AIC in the lymphoid cells the free immunosuppressive agent can become effective causing damage to the specific cell clones.

Animals↗
PubMed1991

[Immunosuppressive acidic protein (IAP) and immunosuppressive substance (ISS) in patients with renal cell carcinoma].

To clarify their usefulness as markers for renal cell carcinoma, serum immunosuppressive acidic protein (IAP) and serum immunosuppressive substance (ISS) were evaluated by TIA (turbidometric immunoassay) for IAP and by SRID (single radial immunodiffusion) for ISS. The mean level of IAP and ISS was beyond each upper normal limit (500, 700 micrograms/ml) in every stage, and especially high in the M1 group. The levels of IAP and ISS were significantly correlated with each other. The determination of IAP and ISS levels after treatment showed a good correlation to the clinical course of the disease. The positive rates of IAP and ISS increased as the stages progressed, respectively. When the influences of pretreatment IAP and ISS level on survival period were investigated, the low IAP or ISS level group (less than two times of the upper normal limit) tended to have a better prognosis than the high level group (more than two times of the upper normal limit) in the M1 patients. These findings suggested that IAP and ISS could be used as markers for monitoring a disease and predicting the prognosis in patients with renal cell carcinoma. As for the positive rate in the combination assay for IAP, TPA and ferritin, or ISS, TPA and ferritin, more than 80% of the patients with low stage renal cell carcinoma had at least one positive marker. This suggested that the combination assay of these three markers was clinically valuable as a disease monitor in patients with renal cell carcinoma.

Adult↗
PubMed1988

Immunosuppression during viral oncogenesis. V. Resistance to virus-induced immunosuppressive factor.

Rabbits given malignant rabbit fibroma virus (MV) develop severe immunologic dysfunction during the course of infection. Splenic T lymphocytes from these rabbits elaborate a soluble non-specific immunosuppressive factor (virus-induced suppressor factor (VISF]. As malignant rabbit fibroma virus infection progresses, normal immunologic responsiveness returns. This recovery is multi-factorial and involves production by T lymphocytes of a soluble factor capable of antagonizing the activity of VISF. This soluble anti-suppressor factor (ASF) is not a generalized immunologic potentiator. Its sole apparent effect on immune function appears to be to antagonize the activity of VISF. The protective effects of ASF are evident only when suppressor factors and ASF are simultaneously present in culture. Pre-treatment of target cells with ASF-containing culture supernatants does not render them insensitive to the immunosuppressive effects of subsequent treatment with VISF. In addition, ASF appears to be directly responsible for antagonizing VISF activity. That is, ASF does not appear to initiate an anti-suppressive cascade by activating a population of cells that in turn generate secondary protective factors. ASF-producing cells do not bind Vicia villosa lectin, as do contra-suppressor cells described by others. In almost all of these features, the system we describe herein differs from systems in which other investigators have described factors that antagonize the effects of suppressor factors.

Animals↗
PubMed1991

Renal allograft immunosuppression. IV. Comparison of lipid and lipoprotein profiles in blood using double and triple immunosuppressive drug combinations.

Serum lipid and lipoprotein profiles were performed in order to investigate lipid abnormalities 2 years post-transplantation in first cadaveric renal allograft recipients immunosuppressed with cyclosporin (CyA), azathioprine (Aza), and methylprednisolone (MP), or with any combination of two drugs. CyA was used in low doses. Total serum cholesterol, triglyceride, LDL cholesterol, HDL cholesterol, HDL2 cholesterol, HDL3 cholesterol, apolipoprotein A1, and apolipoprotein B were determined in 88 prospectively randomized patients with functioning grafts. When considering only the patients who remained on the original randomized treatment, there were no significant differences between the four groups in any of the measured variables. Mean total cholesterol was highest in the group receiving Aza and MP (6.8 mmol/l) and lowest in the group receiving triple therapy (5.8 mmol/l; NS). Mean triglyceride level was highest in the group receiving Aza and MP (2.3 mmol/l) versus 1.8-2.2 mmol/l in the groups receiving triple therapy, Aza + CyA, and CyA + MP. For all patients mean triglyceride level was highest in the group receiving Aza and MP (2.7 mmol/l) and lowest in the group receiving triple therapy (1.7 mmol/l; P less than 0.05). Mean HDL cholesterol ranged from 1.5 to 1.6 mmol/l in all groups. Neither CyA concentration nor CyA or MP dose correlated with cholesterol or triglyceride concentration. However, the average MP dose was twice as high in the group receiving Aza and MP as in the other two groups employing steroids. Serum cholesterol and triglyceride concentrations were related to body mass index (r = 0.28, P = 0.045 and r = 0.30, P = 0.029, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1987

FK-506, a novel immunosuppressant isolated from a Streptomyces. II. Immunosuppressive effect of FK-506 in vitro.

The immuno-pharmacological profile of a novel immunosuppressive agent, FK-506 produced by a streptomycete, is presented here. We proceeded to test the effect of the agent on various in vitro immune systems. It showed that mixed lymphocyte reaction, cytotoxic T cell generation, the production of T cell-derived soluble mediators such as interleukin 2 (IL-2), interleukin 3 and gamma-interferon and the expression of the IL-2 receptor were suppressed by this agent. The IC50 values of FK-506 and ciclosporin (CS) in all tests were approximately 0.1 nM and 10 nM, respectively. Therefore, the novel agent, FK-506 suppressed in vitro immune systems at about hundred times lower concentration than CS.

Animals↗
PubMed1975

Naturally occurring immunosuppressive agents. I. The presence in normal pig liver of a factor possessing immunosuppressive properties with respect to pig lymphoid cells in vitro.

Saline cell-free extracts of normal pig liver, but not normal pig spleen, contain a noncytotoxic factor (or factors) capable of suppressing the blastogenic response of pig lymphocytes to stimulation with a number of plant mitogens: phytohemagglutinin, pokeweed, and concanavalin A. This reaction is generally considered to be a reflection of the capacity of the cell to participate in an immune reaction. Normal pig serum does not display inhibitory activity. The liver extract must be in contact with the lymphocytes for at least the final 48 hr of the 72-hr culture period in order to suppress the blastogenic response. Whether this active constituent in normal pig liver extract is an immunosuppressive agent in vivo remains to be determined.

Animals↗
PubMed1976

[Modification of the immune reaction by antigen-immunosuppressive-agent conjugates. II. Immunogenicity of antigen-immunosuppressive-agent conjugates].

The maintenance of specific immunogenicity of carrier proteins is a necessary condition for the successful use of antigen-immunosuppressive agent-conjugates (AIC) for an antigen specific suppression of the immune response. The experimental results indicate that, in spite of the binding of 6-mercaptopurine (6-MP) and toluyl (T) to bovine gamma globulin (BGG) and human serum albumin (HSA), the carrier specific immunogenicity is not significantly altered. The intradermal application of 6-MP-BGG and T-BGG emulsified with complete Freund's adjuvant in guinea pigs results, in all cases, in a well detectable anti BGG hemagglutination and precipitation titer. This kind of immunization leads also to a formation of anti 6-mercaptopurine and anti new antigen determinants (NAD's) antibodies.

Animals↗
PubMed1976

[Modification of the immune reaction by antigen-immunosuppressive-agent conjugates. IV. Studies on the specific suppression of humoral immune response in guinea pigs by antigen-immunosuppressive-agent conjugates].

Bovine gamma globulin (BGG) antigens were modified by the binding of 6-mercaptopurine and toluyl residues, and their influence on the humoral immune response in guinea pigs was investigated. The antigen-immunosuppressive agent-conjugates (AIC) were different, depending on the method used for their preparation and the number of coupled residues per one molecule of BGG. Conjugates denoted as MPI-n-BGG were prepared by special chemical binding of corresponding thioisocyanates. MPII-n-BGG were synthetized by acetylation, and MPIII-n-BGG conjugates, by reductive alkylation. Pretreatment of guinea pigs with MPIII-19-BGG, MPII-16-BGG resulted in a stimulatory effect on the subsequent humoral immune response induced by BGG application. A significant suppressive influence was detectable if the animals had been pretreated with MPII-6-BGG and MPI-26-BGG. MPI-13-BGG and MPI-36-BGG had no effect on the later induced anti-BGG antibody formation. The immune response against a second antigen (human serum albumin) was not influenced by this kind of pretreatment of the animals. Therefore it seems justified to conclude that both stimulatory and suppressive effects seen here were antigen specific and that both the method for chemical modification and the number of coupled 6-MP residues are very important for their effectivity.

Agglutination↗
PubMed1976

Immunosuppression by Moloney leukemia virus: lack of correlation between virus replication and the immunosuppressive effect.

Young adult mice were infected with 10(4) plaque-forming units (PFU) or Moloney murine leukemia virus M-MuLV. Two different virus preparations were used: a) M-MuLV obtained from serial passage in mice [animal passage (AP)] and b) tissue culture (TC)-grown virus harvested after three in vitro passages of the AP M-MuLV in fibroblasts. Replication of TC and AP M-MuLV in spleen cells was determined by an infectious center (IC) assay at 1 and 2 weeks after the infection. Immune responsiveness of spleen cells was evaluated in challenge with sheep red blood cells (SRBC) and subsequent enumeration of antibody plaque-forming cells (PFC). TC M-MuLV replicated faster in the spleen than did AP M-MuLV and reached about 10- to 100-fold higher titers. However, the response of anti-SRBC PFC, suppressed to the same degree in the spleens of mice infected with TC or AP virus, was from 10 to 50% of the control response. A comparison of virus replication with the anti-SRBC response in aliquots from the same spleens showed no correlation between virus IC and antibody PFC. Both TC and AP M-MuLV induced the expression of virus-specific, cell membrane antigen on spleen cells. These findings indicated a divergence between virus replication on the one hand and the immunosuppressive effect and the cell membrane alteration on the other.

Animals↗