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At least 19 recordsLinked to original sources
PubMedDate not supplied

Enkephalins, brain and immunity: modulation of immune responses by methionine-enkephalin injected into the cerebral cavity.

There is a large number of interactions at molecular and cellular levels between the nervous system and the immune system. It has been demonstrated that the opioid neuropentapeptide methionine-enkephalin (Met-Enk) is involved in humoral and cell-mediated immune reactions. Met-Enk injected peripherally produces a dual and dose-dependent immunomodulatory effect: high doses suppress, whereas low doses potentiate the immune reactivity. The present mini-review concerns the immunological activity of Met-Enk after its administration into the lateral ventricles of the rat brain, and describes the extraordinary capacity of centrally applied Met-Enk to regulate/modulate the immune function. This survey is composed of sections dealing with (a) the role of opioid peptides in the central nervous system (CNS); (b) the activity of opioid peptides in the immune system; (c) the application of Met-Enk into the cerebral cavity; (d) the influence of centrally administered Met-Enk on nonspecific local inflammatory reaction; (e) the effect of Met-Enk injected intracerebroventricularly (i.c.v.) on specific delayed hypersensitivity skin reaction, experimental allergic encephalomyelitis, anaphylactic shock, plaque-forming cell response, and hemagglutinin production; (f) the central antagonizing action of quaternary naltrexone, an opioid antagonist that does not cross the brain-blood barrier, on Met-Enk-induced immunomodulation; (g) the alteration of immune responsiveness by i.c.v. injection of enkephalinase-degrading enzymes; (h) the participation of the brain-blood/blood-brain barrier in the CNS-immune system interaction; and (i) the role of opioid receptors in immunological activity of Met-Enk. A hypothesis has been advanced for the reaction of Met-Enk and opioid receptor sitting on the cell membrane. This concept suggests that the constellation of chemical residues of enkephalin and receptor in the microenvironment determines the binding between the opioid partners. The plurality of conformational structures of enkephalins and receptors makes possible their involvement in a variety of processes which occur in different physiological systems, including the nervous system and the immune system, and intercommunications between the two systems.

Animals↗
PubMed1987

Preclinical and early clinical trial with mafosfamide as immune modulator.

Low doses of cyclophosphamide (CPA) modulate immune responses and induce complete tumor regression and cures in mice. The mechanism of action is related to the development of a T-cell-dependent immune reaction. We started a trial with mafosfamide (MAF), the active metabolite of CPA and found that the response of Ehrlich ascites-tumor (EAT) cells in vivo to this compound is biphasic. The highest cure rate (70%) is obtained with a low i.p. dose of 7 mg/kg/d. Hematologic side effects were not observed. Arguments for an immune mechanism involved are that (1) mice treated with MAF showed a statistically significant increase in spleen weight compared with untreated controls, (2) after treatment large numbers of mononuclear cells appeared in the ascites, and (3) long-term surviving mice were resistant to further challenge with large inocula of EAT. We started a pilot trial in patients with metastasizing and advanced renal cell carcinoma - a disease which can be considered to be influenced by the immunologic response of the tumor host. The starting dose of MAF was 24 mg/m2/d administered i.v. Therapy was repeated at 14 days interval on an out-patient basis. Monitoring of mononuclear cells in the peripheral blood with monoclonal antibodies using a FACS IV were performed two times a week. There are eleven patients on study. Up to now, four out of them have been fully evaluated with respect to toxicity, immune modulation and tumor response. With respect to response to treatment, 2 patients had no change of disease, 1 patient had a mixed and 1 patient a partial response. No hematological or other toxicities could be observed. All patients showed an increase in monocytes/macrophages as well as NK-cells--clearly related to therapy.

Adjuvants, Immunologic↗
PubMed1987

Immune modulators as antiviral agents.

Immune modulators have exhibited some limited efficacy in the prevention or treatment of viral infection. Such agents have included transfer factor, thymosin, thymic humoral factors, levamisole, isoprinosine, immune RNA, young lymphocytes, vitamin C, and BCG. This article focuses on data that have examined clinical application of immune adjuvant therapy.

Adjuvants, Immunologic↗
PubMed1992

Identification of a functionally relevant cannabinoid receptor on mouse spleen cells that is involved in cannabinoid-mediated immune modulation.

Extensive behavioral and biochemical characterization of cannabinoid-mediated effects on the central nervous system has revealed at least three lines of evidence supporting the role of a putative guanine nucleotide-binding protein-coupled cannabinoid receptor for cannabimimetic effects, (i) stereoselectivity, (ii) inhibition of the adenylate cyclase/cAMP second messenger system, and (iii) radioligand-binding studies with the synthetic cannabinoid [3H]CP-55,940 indicating a high degree of specific binding to brain tissue preparations. Based on recent findings from our laboratory demonstrating that delta 9-tetrahydrocannabinol markedly inhibited forskolin-stimulated cAMP accumulation in mouse spleen cells, the presence of a guanine nucleotide-binding protein-coupled cannabinoid receptor associated with mouse spleen cells and its functional role in immune modulation were investigated. In the present studies, stereoselective immune modulation was observed with the synthetic bicyclic cannabinoid (-)-CP-55,940 versus (+) CP-56,667 and with 11-OH-delta 8-tetrahydrocannabinol-dimethylheptyl, (-)-HU-210 versus (+)-HU-211. In both cases, the (-)-enantiomer demonstrated greater immunoinhibitory potency than the (+)-isomer, as measured by the in vitro sheep red blood cell antibody-forming cell response. Radioligand binding studies produced a saturation isotherm exhibiting approximately 45-65% specific binding to mouse spleen cells. Scatchard analysis demonstrated a single binding site on spleen cells, possessing a Kd of 910 pM and a Bmax of approximately 1000 receptors/spleen cell. RNA polymerase chain reaction of isolated splenic RNA using specific primers for the cannabinoid receptor resulted in the amplification of a 854-kilobase predicted product that hybridized with cannabinoid receptor cDNA, demonstrating the presence of cannabinoid receptor mRNA in mouse spleen. Together, these findings strongly support the role of a cannabinoid receptor in immune modulation by cannabimimetic agents.

Animals↗
PubMed1992

Psychoneuroimmunology: can psychological interventions modulate immunity?

There is ample evidence from human and animal studies demonstrating the downward modulation of immune function concomitant with a variety of stressors. As a consequence, the possible enhancement of immune function by behavioral strategies has generated considerable interest. Researchers have used a number of diverse strategies to modulate immune function, including relaxation, hypnosis, exercise, classical conditioning, self-disclosure, exposure to a phobic stressor to enhance perceived coping self-efficacy, and cognitive-behavioral interventions, and these interventions have generally produced positive changes. Although it is not yet clear to what extent these positive immunological changes translate into any concrete improvements in relevant aspects of health, that is, alterations in the incidence, severity, or duration of infectious or malignant disease, the preliminary evidence is promising.

Arousal↗
PubMed1991

Histamine and its congener derivatives as immune modulators.

Our knowledge of the function of histamine as an immunoregulatory autacoid is expanding. The presence of histamine in many tissues in which the immune response takes place and its release during immune response lend credibility to the notion that histamine's role in the immune response could be an important one. In this report we present data that demonstrate the immune modulatory role of histamine. We also describe the synthesis and novel pharmacologic effects of congener derivatives of histamine. These new lymphocyte specific histamine H1 and/or H2 agonists make it feasible to assess the potential of histamine as a selective in vivo immune modulator.

Animals↗
PubMed1986

The effect of RU 41.740, an immune modulating compound, in the prevention of acute exacerbations in patients with chronic bronchitis.

The effect of Biostim (RU 41.740), a new non-specific immune modulator, in reducing the number of acute exacerbations in patients with chronic bronchitis, was examined. One hundred and ninety-eight patients with chronic bronchitis stages 2 and 3 entered the study, which was conducted as a multicenter, double-blind, parallel three-group, placebo-controlled trial. The patients were randomised to placebo, Biostim 2 or 8 mg per day, and received treatment for 1 week every other week for 3 successive months during the winter 1983. A significant (p = 0.005) reduction in the number of acute exacerbations was observed in the patients treated with Biostim 2 mg/day, whereas no effect was observed in the placebo or 8 mg/day group. No serious side-effects were encountered.

Acute Disease↗
PubMed2026

Influence of Major Histocompatibility Complex (MHC) Diversity on Immune Modulation, Pathogenesis, and Control of Lumpy Skin Disease Virus.

INTRODUCTION: Lumpy Skin Disease Virus (LSDV), a member of the genus Capripoxvirus within the family Poxviridae, is an economically important transboundary viral pathogen affecting cattle and water buffalo. The disease causes severe production losses through decreased milk yield, infertility, hide damage, reduced growth performance, and occasional mortality. The rapid geographic spread of LSDV, together with its vectorborne transmission and emerging recombinant strains, has intensified the need for improved understanding of viral pathogenesis, host immune responses, and effective prevention strategies. In particular, the role of the bovine Major Histocompatibility Complex (BoLA/MHC) in regulating antiviral immunity, disease susceptibility, and vaccine responsiveness has gained increasing scientific attention. METHODS: This review summarises the published literature related to the epidemiology, transmission, structure, pathogenesis, diagnosis, prevention, and control of LSDV, with special emphasis on the immunological and molecular role of bovine MHC molecules. Relevant studies concerning BoLA-mediated antigen presentation, immunoinformaticsbased epitope prediction, vaccine development, antiviral drug repurposing, molecular docking, genomic surveillance, and diagnostic approaches, including PCR- and ELISAbased assays, were critically evaluated. Recent advances in computational biology, molecular virology, and host-pathogen interaction studies were also reviewed. RESULTS: The reviewed studies demonstrate that Lumpy Skin Disease Virus (LSDV) possesses a complex double-stranded DNA genome enabling immune modulation and efficient transmission through arthropod vectors such as mosquitoes, ticks, and biting flies. Disease progression involves systemic viral replication, vascular injury, dermal necrosis, and inflammatory skin lesions. Real-time PCR remains the most sensitive diagnostic method for early detection, while ELISA supports surveillance. Evidence highlights the central role of bovine Major Histocompatibility Complex (BoLA) molecules in antigen presentation and T-cell activation. Computational studies identified promising BoLA-binding epitopes and repurposed antiviral candidates, including ivermectin, theaflavin, canagliflozin, and tepotinib, for future therapeutic development. DISCUSSION: Current evidence indicates that effective LSDV control requires integration of molecular diagnostics, vector management, vaccination, and host immunogenetics. BoLAguided immunoinformatics provides promising opportunities for developing multi-epitope vaccines, although experimental validation remains essential. Similarly, repurposed antiviral candidates require comprehensive in vivo and pharmacological evaluation before clinical application. Future research should focus on elucidating viral immune-evasion mechanisms, validating predicted epitopes, and translating computational findings into practical vaccines and therapeutics for sustainable disease control. CONCLUSION: Lumpy Skin Disease continues to pose a major threat to global cattle health and livestock economies. Advances in molecular diagnostics, genomic surveillance, antiviral drug discovery, and BoLA-guided vaccine design provide promising opportunities for improved disease control. Understanding the interaction between LSDV and the bovine MHC system is essential for developing next-generation vaccines, immunotherapeutics, and precision disease-management strategies. Future research should prioritise experimental validation of predicted epitopes, large-scale vaccine trials, and mechanistic studies on host-virus immune interactions to establish effective and sustainable global control programs for LSDV.

BoLA↗
PubMed2026

Biomaterial-Integrated Electroporation for Therapeutic Delivery: From Gene Editing to Tumor Ablation and Immune Modulation.

Electroporation has evolved from a membrane-permeabilization method into a versatile therapeutic platform for intracellular delivery, locoregional tumor intervention, and bioelectrically regulated treatment. Depending on pulse intensity and duration, electroporation operates in two distinct modes: reversible electroporation (RE), which transiently permeabilizes the plasma membrane to enable delivery of nucleic acids, proteins, and small molecules while preserving cell viability, and irreversible electroporation (IRE), which causes permanent membrane damage for non-thermal tissue ablation. Increasingly, the therapeutic scope of electroporation is being expanded through integration with biomaterials, including nanocarriers, hydrogels, soft conductors, and micro/nanoengineered bioelectronic interfaces. These material-assisted strategies improve cargo protection, field confinement, local retention, tissue conformity, and spatiotemporal control, thereby extending electroporation beyond conventional transfection toward gene editing, engineered cell manufacturing, electrochemotherapy, tumor ablation, immune modulation, and transdermal or localized delivery. In this Review, we summarize the biophysical principles of RE and IRE, discuss how biomaterials reshape electroporation performance across therapeutic settings, compare the design logic of major biomaterial-assisted electroporation platforms, and highlight key translational challenges, including pulse-material compatibility, manufacturing scalability, in vivo dosimetry, and regulatory complexity.

Humans↗
PubMed1990

Antiviral activity of the novel immune modulator 7-thia-8-oxoguanosine.

A novel thiazolopyrimidine nucleoside, 5-amino-3-beta-D-ribofuranosylthiazolo[4,5-d]pyrimidine-2,7(3H,6H) -dione (7-thia-8-oxoguanosine), was evaluated for antiviral activity in rodent models, and at 50-200 mg/kg prevented death in mice inoculated intraperitoneally (i.p.) with Semliki Forest, San Angelo, and banzi viruses when administered i.p. before virus challenge. Similarly, the nucleoside was effective against an intranasal challenge of rat coronavirus in suckling rats, with activity present when treatment started as late as 4 h after virus inoculation. Protection was observed against herpes type 1 and murine cytomegalovirus (both inoculated i.p.) infections, and encephalitis induced by intracerebral inoculation of a human coronavirus in mice. Friend leukemia virus splenomegaly was more severe in drug-treated animals than in placebos. This immune modulator is promising for the treatment of animal and human diseases.

Adjuvants, Immunologic↗
PubMed1987

Immune modulation by danazol in autoimmune thrombocytopenia.

Danazol, an attenuated androgen, has recently been introduced into the treatment of autoimmune thrombocytopenia. We studied its effects on T helper/inducer (Thi) and T suppressor/cytotoxic (Tsc) lymphocytes in these patients. Prospectively nine patients were studied with their T-cell subsets measured before and during danazol therapy. Increases in the percentage of Thi lymphocytes (P less than 0.05) and Thi/Tsc ratios (P less than 0.001) were observed at 1 and 3 months of treatment. Retrospectively T-cell subset data on 30 patients not treated with danazol and 36 patients on danazol were compared with those of 35 normal controls. The group not on danazol had lower percentages of Pan T (P less than 0.05), Thi (P less than 0.002), and Thi/Tsc ratios (P less than 0.00005), and had higher percentages of Tsc lymphocytes (P less than 0.01), than those of controls. In the group treated with danazol the percentages of Pan T, Thi, and Tsc lymphocytes were similar to those of controls. The percentage of Thi in the treated group was higher (P less than 0.002) than in the untreated group. Thus, danazol appears to be an effective immune modulator, correcting the abnormality of T-cell subsets seen in autoimmune thrombocytopenia by increasing the percentage of Thi lymphocytes.

Autoimmune Diseases↗
PubMed1976

[Therapy of inflammatory-rheumatic diseases with levamisol, an immunity modulating substance].

Since cellular and humoral immune mechanisms were shown to be involved in the pathogenesis of rheumatic diseases, efforts have been made to influence these systems therapeutically. Aside from suppression of the immune response, studies have been conducted to evaluate to what extent immunostimulation might be of value in the treatment of rheumatic diseases. Levamisole, chemically a simple synthetic agent recently shown to have immunorestorative capacities in anergic cancer patients, has been administered in several rheumatic diseases. The drug was administered either continuously or intermittently in a daily dose of 150 mg over several months. In about half of the rheumatoid arthritis patients a significant improvement was noted. Beneficial effects and sometimes even dramatic improvement lere observed in some patients with systemic lupus erythematosus, ankylosing spondylitis and Reiter's syndrome. Levamisole did not alter the course of psoriatic arthritis. Significant adverse reactions were leukopenia and allergic skin reactions. Other side effects were mild and did not require interruption of drug intake. The use of levamisole in rheumatic diseases is still experimental, but with accumulating experience it may provide a true improvement in control of rheumatic diseases.

Arthritis↗
PubMed1991

Enkephalinase-inhibitors modulate immune responses.

Exogenous opioid peptides, and enkephalins in particular, modulate a variety of immune performances in vivo and in vitro. In this study, the immunomodulatory role of endogenous opioids was investigated by means of central and peripheral administration of four peptidase inhibitors in the rat. Animals sensitized with sheep red blood cells (SRBC) were daily treated intraperitoneally (i.p.) with 0.2 mg/kg or 1 mg/kg of each inhibitor, or intracerebroventricularly (i.c.v.) with 0.02 mg/kg and 0.2 mg/kg of bestatin, des-tyrosine-methionine-enkephalin, (Des-Tyr1)Met-Enk; and actinonin, and 0.005 and 0.5 mg/kg of N-Carboxymethyl-phenilalanine-leucine,(N-C)Phe-Leu. Controls were injected i.p. and i.c.v. with saline. The results revealed that in animals treated i.p. with 0.2 mg/kg of bestatin and (N-C)Phe-Leu potentiated the plaque-forming cell (PFC) response and hemagglutinin production. In contrast, these immune responses were suppressed by 1 mg/kg. On the other hand, i.p. doses of 0.2 and 1 mg/kg of actinonin and (Des-Tyr1)Met-Enk potentiated humoral immune responses. When given i.c.v., all of the inhibitors used exerted clear dose-dependent immunomodulatory effects, i.e. increase in the PFC response and hemagglutinin production when given at lower doses (0.005-0.02 mg/kg), and decrease when injected with higher doses (0.2-0.5 mg/kg). These effects of enkephalin-related peptidase inhibitors, applied i.p. and i.c.v., suggest the involvement of endogenous enkephalins in immune mechanisms.

Adjuvants, Immunologic↗
PubMed1990

Immunity to sexual stages of human malaria parasites: immune modulation during natural infections, antigenic determinants, and the induction of transmission-blocking immunity.

Four antigens of Plasmodium falciparum have so far been identified as targets of transmission-blocking antibodies; three of them (Pfs 230, 48/45) are detectable in gametocytes and expressed on gametes, the fourth (Pfs 25) appears only after fertilization. Epitope analyses of each antigen were made with competitive immunoassays, and the extent of antigenic diversity determined amongst numerous isolates of P. falciparum. There was minimal variation within one of the two epitopes on Pfs 230 both of which induce transmission-blocking antibodies. The epitopes on Pfs 25 to which blocking monoclonal antibodies respond showed a variability amongst different isolates by immunofluorescence which was unexpected in view of sequence data on the molecule. Five epitope regions have been identified on Pfs 48/45 and antibodies to them interact in a complex manner. Antigenic diversity affecting these epitopes was minimal. In P. vivax malaria much greater polymorphism was seen amongst gamete surface antigens. Natural P. falciparum infections induce antibody responses to gametocyte/gamete surface antigens that will suppress infectivity to mosquitoes but these responses may involve reactivity with any of a series of different epitopes, interactions between antibodies, and may be sequential. In P. vivax infections antibody to the sexual stage antigens may suppress or enhance transmission depending on the antibody level. Cytokine production induced by sexual stage antigens may also modulate transmission, by rendering gametocytes non-infective. Experimental studies showed marked MHC-restriction of immune responses to gamete antigens (but not to the Pfs 25 zygote antigen); the evidence from studies in humans is less convincing. Antibody responses to the sexual stage antigens seem to be more frequent in persons who have experienced only one or a few attacks of malaria as opposed to those who have been exposed frequently. Some form of down-regulation may therefore be occurring.

Animals↗
PubMed1991

Immune modulation and cancer.

The concept that the immune system is involved in defence against cancer goes back nearly a hundred years. Despite increased sophistication in our analysis of the immune response it has proven difficult to demonstrate a powerful role of the immune system in either the prevention or treatment of cancer. Animal data has consistently and clearly shown that the immune system can identify and reject experimental tumours. In patients the data is more conflicting. The isolation of individual cytokines which stimulate specific components of the immune response and have a anti-cancer effect does suggest, however, that as we learn more about the interaction between immunity and cancer, novel methods for the diagnosis and therapy of cancer will be developed.

Antigens, Neoplasm↗
PubMedDate not supplied

Immune modulation and disease patterns in population groups.

A hypothesis which explains disease prevalence among different socio-economic groups following early infantile modulation of cell-mediated immunity by infection and nutrition related stress is presented. Wealthy populations living under highly hygienic circumstances can develop their cell-mediated immunity to genetic expectation while their humoral systems remains unstimulated. Primitive populations protect the infant's immune development by breast feeding and suffer from temporary cell-mediated immune deficiencies due to intercurrent infectious disease and famine later on. Intermediary populations harbour a small percentage of people, whose cell-mediated immune system has been permanently damaged by infection in early childhood, leading to a high incidence of diseases linked to cell-mediated immune deficiency. The possible cocarcinogenesis of the cell-mediated immune deficiency following repeated gastroenteritis and persistent stimulation of B cells, leading to alpha heavy chain disease and primary intestinal lymphoma, or due to falciparum malaria in newborns and its impact on the EB virus genome in development of Burkitt's lymphoma, are discussed.

Africa↗
PubMed1992

Immune modulating effects of low doses of cyclophosphamide and keyhole limpet hemocyanin on peripheral blood immune parameters in patients with metastatic renal cell carcinoma.

Assessing the peripheral blood immune status, we had found evidence of immunosuppression in metastatic renal cell carcinoma. Since immunosuppression might interfere with the outcome of immunotherapy, it was submitted to further investigation. Immunosuppression can be mediated by T suppressor cells, which for their part are inhibited by low-dose cyclophosphamide (Cy). We tested whether the immunomodulating effects of the biological response modifier keyhole limpet hemocyanin (KLH) on cellular and humoral immune parameters would be intensified by low-dose Cy. 10 patients were given 300 mg/m2 Cy i.v. 3 days before application of 1 mg KLH i.m. up to 8 times in 4-weekly intervals. Immune parameters were assayed twice pre-therapeutically, and prior to and 1 day and 1 week after each KLH injection. In contrast to the results obtained with KLH-mono-application, lymphocyte subsets-with the exception of T4 cell counts and the T4/T8 ratio-remained stable during the first 4 months of observation. There were increases in immunoglobulins and in the immunoactivation markers tumor necrosis factor, neopterin and beta 2-microglobulin. The tendencies found here differed from those found in a previous study on patients who were given KLH alone, and were similar to those found in patients with nonmetastatic disease who received KLH alone. However, the increases of the activation markers during KLH+Cy application were at best half as much as in patients with nonmetastatic disease. In conclusion, immunosuppression was influenced, but not counterbalanced by low-dose Cy. Most probably other mediators of immunosuppression than T suppressor cells, for example prostaglandin E2, must be considered as well.(ABSTRACT TRUNCATED AT 250 WORDS)

Adjuvants, Immunologic↗
PubMed1988

Opioid peptides modulate immune functions. A review.

In the past few years it has become evident that neuropeptides may be direct mediators in the modulation of the immune response and the unspecific defense by the brain. Lymphocytes have been thought to have opioid receptors and to respond to opioids with an increase in blastogenesis, cytotoxicity and factor release. Lymphocytes are said to release various neuropeptides. Furthermore, there are some unexplained effects of morphine on the immune system and of the immune system on morphine withdrawal. The purpose of this paper is to review what has been previously published in this field. The well established modulation of phagocyte functions by opioids will only be scanned.

Animals↗