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Biomedical subjects

I Berczi

Publications and source records attributed to I Berczi.

At least 19 recordsLinked to original sources
PubMed2001

The thymus and the acute phase response.

The thymus is a primary lymphoid organ with both endocrine and immune functions. There is a large body of evidence indicating the existence of a complex neuroendocrine control of the thymus physiology. This is supported by the historic observation that the thymus becomes involuted during the response to stress. The thymus is dramatically affected by the acute phase response (APR), a systemic reaction to tissue injury and/or infection accompanied by profound neuroendocrine and metabolic changes. The APR comprises alterations in behavior, body temperature, and production and release of cytokines, particularly interleukin (IL)-1, IL-6 and TNFalpha, and glucocorticoids (GCs) and is characterized by suddenly increased production of so-called acute phase proteins (APPs). The stimulation of APR activates the hypothalamic-pituitary-adrenal (HPA) axis, resulting in the suppression of specific immunity, which might serve to protect the organism from adverse immune reactions; the immunostimulatory hormones (e.g., PRL, GH, IGF-1) are suppressed, whereas the production of APPs in the liver is stimulated by IL-6, catecholamines and GCs. The most striking effect of the latter on the immune system is the induction of apoptosis in the thymus. In concert with GCs, elevated levels of catecholamines also selectively suppress immune response mechanisms. APR may be regarded as an emergency response that represents a switch of the host defense from the adaptive immune response which is slow to develop and is commanded by the thymus and T-lymphocytes to a less specific, but more rapid and intense reaction. Here we discuss the immunoregulatory changes during the APR with a special emphasis on the role of thymus in this process.

Acute-Phase Reaction↗
PubMed2000

Natural immunity and neuroimmune host defense.

Innate resistance is mediated by non-immune defense and by natural immunity. Non-immune defense includes diverse mechanisms (e.g., physico-chemical defense by bile acids). Natural killer (NK) cells, gamma delta T lymphocytes and CD5+ B lymphocytes are key mediators of natural immunity. These cells utilize germ-line coded receptors that recognize highly conserved, homologous epitopes (homotopes). Typically, it is not the antigen, but cytokines and hormones that regulate the level of NK-mediated cytotoxicity. These include interleukin-2, interferons, prolactin and growth hormone. Less is known about gamma delta T lymphocytes. CD5+ B lymphocytes produce germ-line coded antibodies (predominantly IgM) that are polyspecific, and able to recognize a great variety of microorganisms, cancer-cells and self-components. Antigen is not an effective stimulus for natural antibody (NAb), but bacterial lipopolysaccharide (LPS) is. During the acute phase response (febrile illness) the T-cell-regulated adaptive immune response is switched off and natural immune mechanisms are amplified several hundred to a thousand times within 24-48 hours (immunoconversion). This immunoconversion is initiated by immune-derived cytokines, and involves profound neuroendocrine and metabolic changes, all in the interest of host defense. Immune recognition is assured by natural antibodies and by some liver-derived acute phase proteins, such as C-reactive protein or endotoxin-binding protein, the level of which is elevated in the serum. Thus, natural immunity is essential for a first and last line of defense and the neuroendocrine system is an important promoter of this activity.

Animals↗
PubMed2000

Suppression of lymphocyte mitogenesis by tamoxifen: studies on protein kinase C, calmodulin and calcium.

The effect of tamoxifen (TX; 1.0 microM) on the mitogenic response of rat lymphocytes was compared with the effect of drugs that are known to act on protein kinase C (PKC), calmodulin (CM), and calcium (Ca(2+)). The calcium ionophore A23187 (0.2 microM) was mitogenic on its own which was not influenced by TX. The agents modulating PKC or CM (phorbol-myristate-13-acetate; R24571, chlorpromazine) influenced mitogenesis differently than did TX. General inhibition of lymphocyte proliferation was seen with the Ca(2+) antagonist agents (EGTA, TMB-8) as with TX. The antiproliferative effect of TX was partially reversed by the increase of Ca(2+) in the culture medium when T cell mitogens were used, but not in the case of lipid A, a B lymphocyte mitogen. However, the concanavalin A-induced Ca(2+) influx was further elevated by TX which differed from the effect of the Ca(2+) channel-blocking agent verapamil. The results suggest that TX resets the threshold stimulus necessary for mitogenesis and is completely reversible.

Animals↗
PubMed1998

The stress concept and neuroimmunoregulation in modern biology.

Sixty years ago Hans Selye discovered that the neuroendocrine and immune systems interact during stress. The pathophysiological significance of neuroendocrine-immune interaction during injury has only been recognized recently. Today it is rapidly emerging that, in addition to defense against exogenous pathogenic agents, the immune system plays a key role in host defense against injury. During acute-phase reactions to infection/injury, when there is no time to mount a specific immune response, the neuroimmunoregulatory network suppresses specific immunity while rapidly elevating the production of acute-phase proteins (APP) in the liver. APP recognize microbes and abnormal cells/tissues and activates the immune system nonspecifically to fight infection or injury. There is a remarkable similarity between the stress syndrome as outlined by Selye in 1946 and the acute-phase response as we know it today. Moreover, it is becoming clear that the immune system participates in the normal physiological regulation of the body, which was also recognized by Selye in his later years. Although with much delay, the scientific community is beginning to fully appreciate Selye's ingenious discoveries which were far ahead of his time.

Acute-Phase Reaction↗
PubMed1998

Neurohormonal host defense in endotoxin shock.

Lipopolysaccharide (LPS) of gram-negative bacteria is capable of activating the immune system of higher animals, which may lead to cytokine-induced lethal shock and death. LPS has little toxicity for the frog and fish, but it kills the horseshoe crab instantly by causing intravascular blood coagulation. The response to LPS evolved from simple reactions in lower animals into an intense reaction in mammals that involves a massive immune activation leading to a profound neuroendocrine and metabolic response. This is now known as the acute-phase response (APR). During APR, LPS-binding proteins (LBP) are produced by the liver in rapidly increasing quantities under the influence of interleukin-6, glucocorticoids, and catecholamines. After combination with LPS, LPB is capable of activating monocyte-macrophages and granulocytes via the CD14 surface receptor. Other receptors (CD18, 80-kDa receptor) allow for direct action by LPS of phagocytes, B and T lymphocytes, and other cells. Numerous other acute-phase proteins are produced in the liver, including C-reactive protein, complement components, fibrinogen, enzyme inhibitors, and anti-inflammatory proteins. Similar responses may be stimulated by subtoxic doses of LPS or by detoxified LPS, which manifest in endotoxin tolerance. Tolerant animals and man show increased resistance to LPS, to infections, and to various noxious insults. Infection and various forms of tissue injury are also capable of causing APR. There is much evidence to indicate that APR, which manifests in febrile illness, is an efficient host defense reaction. It is an emergency response in cases where specific immunity fails to protect the host. Therefore, the neuroimmunoregulatory network converts the immune system to a less specific, but rapid and more efficient response, APR. The hypothesis is presented that intestinal LPS serves to amplify the APR in response to various insults, which contribute to host defense, regeneration, and healing.

Animals↗
PubMed1998

Neuroimmunoregulation and natural immunity.

The development and function of the immune system is regulated by neuroendocrine factors. Immune function may be divided into adaptive and natural immunity. Adaptive immune responses are driven by specific determinants of the antigen (epitopes), require 5-10 d to fully develop, and show an accelerated or memory response after repeated exposure to the same antigen. Natural immunity may be divided into host defense mediated by non-immune factors (e.g., antimicrobial proteins, enzymes, mucus etc.) and polyspecific responses of the immune system. This polyspecific response relies on natural antibodies and on some other serum proteins (e.g., lipopolysaccharide-binding protein-LBP, C-reactive protein-CRP), and on surface receptors of macrophages, natural killer cells and B and T lymphocytes for activation. Highly conserved homologous (crossreactive) epitopes, or homotopes for short, are recognized by the natural immune system. Natural antibodies, LBP, and CRP are capable of activating the entire immune system after combination with the appropriate homotope. During febrile illness natural immune host defense is promptly elevated because of the rapid rise of natural antibodies, LBP, and CRP in the serum. This is known as the acute phase response (APR), which is initiated by a sudden rise of cytokines in the circulation, such as IL-1, IL-6, and TNF-alpha. The cytokines act on the brain, the neuroendocrine system, and on other tissues and organs, which leads to fever and profound hormonal and metabolic changes. The hypothalamus-pituitary adrenal axis is activated and serves as the primary regulator of immune and inflammatory reactions. Insulin, glucagon, and catecholeamine levels are also raised. Bone marrow activity and leukocyte function are high and the liver is converted to the rapid production of acute-phase proteins (APP). APP include LBP, CRP, fibrinogen, some complement components, enzyme inhibitors, and anti-inflammatory proteins, which may rise in the serum from several hundred to a thousand times within 24-48 hr. Therefore, natural immunity is a polyspecific response to homotopes, which functions as an instantaneous defense mechanism in health and which is rapidly boosted by cytokines and hormones during febrile illness. This is a highly successful defense reaction, as in the overwhelming majority of cases, febrile illness leads to recovery and the development of adaptive immunity in man and higher animals.

Acute-Phase Reaction↗
PubMed1998

Neuroimmunoregulation and cancer (review).

It is certain that neuroimmune mechanisms play a role in host defence against cancer. However, this interaction is highly complex and many variations are possible according to the nature of the neoplasms involved. There are indications that adaptive immunity is present in a significant proportion of tumor bearing hosts, and this defence may be boosted by specially designed vaccines and cytokines. Natural immune mediators are also implicated in resistance against tumor development. Here we review the evidence suggesting that hormonal manipulation of the host can result in the elevation of immune defences against cancer. Such manipulation strengthens both the adaptive and natural immune defences of the host, both of which play significant roles. Natural defence mechanisms are boosted by cytokines and hormones during febrile reactions which are now known as the acute phase response. It is suggested that hormonal stimulation of immune mechanisms coupled with the usual immunostimulants already in use may be employed to good advantage for the combination immunotherapy of cancer. Modern molecular biology approaches permit the development of laboratory monitoring procedures which may be used for the prediction and follow-up of therapeutic success.

Acute-Phase Reaction↗
PubMed1997

Pituitary hormones and immune function.

The pituitary gland plays a key role in the regulation of growth, differentiation and function of all cells in the body, including immunocytes. Immune reactions are generated through the proliferation of antigen-specific lymphocyte clones. Growth hormone and prolactin are required for the development of mature lymphocytes and for the maintenance of immunocompetence. These hormones enable lymphocytes to respond to antigen, which is delivered as an adherence signal in the context of major histocompatibility surface molecules of antigen-presenting cells. Numerous other adhesion molecules play a role in the regulation of lymphocyte activation. The activation process is completed by cytokine signalling, after which lymphocyte proliferation, differentiation and functional maturation take place. Interleukins, hormones and growth factors may all function as cytokines. Many lymphocytes exist in the body in a quiescent state, with minimal metabolic activities. These cells are maintained by competence hormones and insulin-like growth factor 1, which are present in the systemic and local environment. Apparently, some steroid hormones, opioid peptides and catecholamines are capable of modulating delivery of the signal from the lymphocyte membrane receptor to the nucleus. Steroid and thyroid hormones control nuclear transcription factors as their receptors, and thus are powerful regulators of lymphocyte signalling at the nuclear level. The bioactive forms of thyroid hormone and of several steroid hormones are generated locally by immunocytes. These important hormonal immunoregulators function both at systemic and local levels. Glucocorticoids are major regulators of cytokine production, and alpha-melanocyte-stimulating hormone functions as a powerful cytokine antagonist. The hormones secreted or regulated by the pituitary gland therefore regulate every level of immune activity, including the competence of lymphocytes to respond to immune/inflammatory stimuli, signal transduction, gene activation, the production and activity of cytokines and other immune effector functions.

Animals↗
PubMed1996

Neuroimmune mechanisms in health and disease: 2. Disease.

In the second part of their article on the emerging field of neuroimmunology, the authors present an overview of the role of neuroimmune mechanisms in defence against infectious diseases and in immune disorders. During acute febrile illness, immune-derived cytokines initiate an acute phase response, which is characterized by fever, inactivity, fatigue, anorexia and catabolism. Profound neuroendocrine and metabolic changes take place: acute phase proteins are produced in the liver, bone marrow function and the metabolic activity of leukocytes are greatly increased, and specific immune reactivity is suppressed. Defects in regulatory processes, which are fundamental to immune disorders and inflammatory diseases, may lie in the immune system, the neuro endocrine system or both. Defects in the hypothalamus-pituitary-adrenal axis have been observed in autoimmune and rheumatic diseases, chronic inflammatory disease, chronic fatigue syndrome and fibromyalgia. Prolactin levels are often elevated in patients with systemic lupus erythematosus and other autoimmune diseases, whereas the bioactivity of prolactin is decreased in patients with rheumatoid arthritis. Levels of sex hormones and thyroid hormone are decreased during severe inflammatory disease. Defective neural regulation of inflammation likely plays a pathogenic role in allergy and asthma, in the symmetrical form of rheumatoid arthritis and in gastrointestinal inflammatory disease. A better understanding of neuroimmunoregulation holds the promise of new approaches to the treatment of immune and inflammatory diseases with the use of hormones, neurotransmitters, neuropeptides and drugs that modulate these newly recognized immune regulators.

Acquired Immunodeficiency Syndrome↗
PubMed1996

Neuroimmune mechanisms in health and disease: 1. Health.

A novel scientific discipline that examines the complex interdependence of the neural, endocrine and immune systems in health and disease has emerged in recent years. In health, the neuroimmunoregulatory network is fundamental to host defence and to the transfer of immunity to offspring; the network also plays important roles in intestinal physiology and in tissue regeneration, healing and reproduction. The proliferation of lymphocytes in primary lymphoid organs (bone marrow, bursa of Fabricius [in birds] and thymus) and in secondary lymphoid organs (spleen, lymph nodes and mucosal lymphoid tissue) depends on prolactin and growth hormone. These hormones allow immune cells to respond to antigen and to soluble mediators, called cytokines. Immune-derived cytokines are capable of inducing fever and of altering neuro-transmitter activity in the brain and hormone secretion by the pituitary gland. The activation of the hypothalamus-pituitary-adrenal axis by cytokines leads to immunosuppression. Lymphoid organs are innervated, and tissue mast cells respond to neurologic stimuli. In general, acetylcholine and substance P exert immunostimulatory and proinflammatory effects, whereas epinephrine and somatostatin are immunosuppressive and anti-inflammatory. In this article, the authors predict that novel approaches to immunomodulation will be possible by altering the level or efficacy of immunoregulatory hormones and neurotransmitters.

Humans↗
PubMed1996

Anti-estrogens enhance the therapeutic effect of lymphokine-activated killer cells on the P815 murine mastocytoma.

Tamoxifen (TX) and toremifene (TO) enhanced the lysis of P815 mastocytoma cells in vitro by syngeneic DBA2 spleen cells that have been activated by human recombinant interleukin-2 (IL-2) for 6 days (lymphokine-activated killer [LAK] cells). Similarly, enhanced tumor suppression occurred when TX- or TO-treated P815 cells were mixed with LAK cells and injected s.c. into normal DBA2 recipients. Tumor suppression could be increased further by treating such recipients orally with TX or TO and by the repeated injections of LAK cells into the tumor site. The treatment of animals bearing tumors (5 mm in diameter) orally with TX or TO or with LAK cells i.p. resulted in tumor suppression. When the drug treatment was combined with LAK cells, tumor suppression was more pronounced, and complete tumor regression was induced in a significant number of the animals so treated. Our results indicate that the immunotherapeutic effect of LAK cells can be significantly amplified by combined treatment with the anti-estrogens TX or TO.

Analysis of Variance↗
PubMed1996

Modulation of lymphokine-activated killer cell-mediated cytotoxicity by estradiol and tamoxifen.

The effect of tamoxifen (TX) and estradiol (E2) on interleukin-2 (IL-2 )-activated killer (LAK) cell-mediated cytotoxicity was examined using spleen cells of Fischer 344 rats as the source of effectors and P815 murine mastocytoma cells as targets. Treatment of target cells with either TX or E2 for 4 or 18 hr rendered them highly sensitive to LAK cell-mediated lysis. When TX and E2 were applied jointly, cytotoxicity remained at the level of TX alone. The cytotoxic potential of IL-2-primed LAK cells was not modified consistently by TX and E2. When TX-treated target and effector cells were combined, high cytotoxicity characteristic of sensitized target cells was observed. In similar experiments with E2-treated cells, both enhancement and inhibition of cytotoxicity by treated effector cells was seen in some designs. Target cells could be sensitized for LAK cell-mediated destruction by physiological concentrations (1 nM) of E2 and equimolar concentration of TX. Sensitization led to the accelerated release of the nuclear label 3H-thymidine from target cells after cytotoxic insult and could be prevented by treatment with the metabolic inhibitors cycloheximide and actinomycin D. Enhanced 3H-thymidine release from TX-treated targets was also demonstrated after induction of Ca2+ influx by exposure to the ionophore A23187. Neither E2 nor TX exerted a direct cytotoxic effect on P815 cells. P815 cells had no classical receptors for E2 or progesterone.

Animals↗
PubMed1996

The immune effects of neuropeptides.

Current evidence indicates that the neuroendocrine system is the highest regulator of immune/inflammatory reactions. Prolactin and growth hormone stimulate the production of leukocytes, including lymphocytes, and maintain immunocompetence. The hypothalamus-pituitary-adrenal axis constitutes the most powerful circuit regulating the immune system. The neuropeptides constituting this axis, namely corticotrophin releasing factor, adrenocorticotrophic hormone, alpha-melanocyte stimulating hormone, and beta-endorphin are powerful immunoregulators, which have a direct regulatory effect on lymphoid cells, regulating immune reactions by the stimulation of immunoregulatory hormones (glucocorticoids) and also by acting on the central nervous system which in turn generates immunoregulatory nerve impulses. Peptidergic nerves are major regulators of the inflammatory response. Substance P and calcitonin gene-related peptide are pro-inflammatory mediators and somatostatin is anti-inflammatory. The neuroendocrine regulation of the inflammatory response is of major significance from the point of view of immune homeostasis. Malfunction of this circuit leads to disease and often is life-threatening. The immune system emits signals towards the neuroendocrine system by cytokine mediators which reach significant blood levels (cytokine-hormones) during systemic immune/inflammatory reactions. Interleukin-1, -6, and TNF-alpha are the major cytokine hormones mediating the acute phase response. These cytokines induce profound neuroendocrine and metabolic changes by interacting with the central nervous system and with many other organs and tissues in the body. Corticotrophin releasing factor functions under these conditions as a major co-ordinator of the response and is responsible for activating the ACTH-adrenal axis for regulating fever and for other CNS effects leading to a sympathetic outflow. Increased ACTH secretion leads to glucocorticoid production. alpha-melanocyte stimulating hormone functions under these conditions as a cytokine antagonist and an anti-pyretic hormone. The sympathetic outflow, in conjunction with increased adrenal activity. leads to the elevation of catecholamines in the bloodstream and in tissues. Current evidence suggests that neuroimmune mechanisms are essential in normal physiology, such as tissue turnover, involution, atrophy, intestinal function, and reproduction. Host defence against infection, trauma and shock relies heavily on the neuroimmunoregulatory network. Moreover, abnormalities of neuroimmunoregulation contribute to the aetiology of autoimmune disease, chronic inflammatory disease, immunodeficiency, allergy, and asthma. Finally, neuroimmune mechanisms play an important role in regeneration and healing.

Animals↗
PubMed1995

Modulation of natural killer cell-mediated cytotoxicity by tamoxifen and estradiol.

BACKGROUND: The nonsteroidal antiestrogenic drug, tamoxifen, inhibits the growth of estrogen receptor-positive tumors by interfering with the growth-stimulatory effect of estradiol. However, there is compelling evidence that tamoxifen treatment also is beneficial for patients with estrogen receptor-negative tumors. The hypothesis that tamoxifen is capable of enhancing the immunologic defense of tumor-bearing hosts was been investigated as a possible method for targeting receptor-negative neoplasms. METHODS: Natural killer (NK) cells in the spleen of female Fisher and Wistar-Furth rats were used against the YAC-1 murine lymphoma target in 51Cr-release assays. The effect of various concentrations of estradiol and tamoxifen (1 nM-1 microM) and of the metabolic inhibitors actinomycin D and cyclohexamide on target-cell killing was investigated. RESULTS: Tamoxifen enhanced and estradiol inhibited killing if applied for the entire 5 hours of the cytotoxic reaction. When applied jointly in this experimental setup, estradiol interfered with the enhancing effect of tamoxifen. Pretreatment of target cells with tamoxifen led to highly significant enhancement of cytotoxicity; estradiol also enhanced target cell killing, but to a lesser extent. After joint treatment, the level of cytotoxicity was comparable with that obtained with tamoxifen alone. Both pharmacologic (100 nM and 1 microM) and physiologic (1 or 10 nM) concentrations of estradiol and equimolar tamoxifen enhanced target cell lysis. However, pharmacological levels of estradiol inhibited effector cells when applied alone or in combination with tamoxifen. Highly significant enhancement of target-cell destruction occurred if both target and effector cells were pretreated with tamoxifen, whereas estradiol treatment of both cell types led to slight enhancement or no effect on cytotoxicity. Treatment of the target cells with actinomycin D or cycloheximide inhibited the lysis of untreated and tamoxifen- or estradiol-exposed cells. Treatment of YAC-1 target cells with tamoxifen or estradiol also enhanced the NK cell-mediated release of the nuclear label, 3H-thymidine, indicating DNA degradation. Similarly treated P815 cells resisted lysis by NK cells, but showed sensitization when the NK cells were stimulated by interleukin-2 for 48 hours before the lytic reaction. Estradiol and tamoxifen changed the kinetics of 3H-thymidine incorporation by YAC-1 cells, but the cells were capable of growing with the highest drug concentrations (1 microM) used in the cytotoxicity experiments. YAC-1 cells have no cytosolic estradiol receptors and are weakly positive for cytosolic progesterone receptors. CONCLUSIONS: These experiments indicate that NK cell-mediated target-cell destruction can be enhanced by tamoxifen primarily through sensitizing the target for lysis. Estradiol also sensitizes the target but inhibits the effector cells simultaneously so that little or no change results in cytolysis. Target-cell sensitization is not mediated by classical estrogen receptors and requires the active metabolic participation of the cells treated. A likely mechanism of this phenomenon is priming the target cell for apoptosis.

Animals↗
PubMed1994

Target cells are sensitized for cytotoxic T-lymphocyte-mediated destruction by estradiol and tamoxifen.

The effect of estradiol (E2) and tamoxifen (TX) on cytotoxic T-lymphocyte (CTL)-mediated target-cell lysis was studied. CTL was generated in mixed cultures of rat spleen cells, using female Fischer 344 rat cells as responders and female Wistar rat cells or Nb2 rat lymphoma cells as stimulators. Concanavalin-A-stimulated Wistar lymphoblasts or Nb2 cells were used as targets. CTL harvested on day 5 exerted 16-25% cytotoxicity when used at 1:12-1:50 target:effector cell ratios. Day-6 CTL had no cytotoxic activity. Treatment of target cells with either TX or E2, or both, at 1-microM concentrations for 4 hr prior to cytotoxicity testing raised the target-cell killing to 100%. Highly significant enhancement of cytotoxicity was also observed when the drugs were used at 100-, 10-, or 1-nM concentrations. Treatment of effector cells under similar conditions led to inhibition of cytotoxicity at 1-microM concentration, some enhancement at 100 nM and no effect at 10 and 1 nM. When treated target and effector cells were combined, the amplification of target-cell lysis was similar in magnitude to that seen in tests with treated targets only. Drug treatment of target cells had no influence on their resistance to lysis in hypotonic solutions or on total and spontaneous 51Cr release. The inhibition of DNA and protein synthesis in target cells interfered with both basal cytolysis and drug-induced enhancement. The release of the nuclear label, [3H]-thymidine, from Nb2 targets by CTL, was also enhanced by target treatment with TX. These results illustrate that CTL-mediated cytotoxicity is amplified by physiological concentrations (1 and 10 nM) of E2 and equimolar concentrations of TX.

Animals↗
PubMed1993

Production and characterization of monoclonal antibodies to embryo-associated immunosuppressor factor (EASF) produced by human pre-implantation embryo.

Balb/c mice were immunized with pre-implantation embryo-associated immunosuppressor factor (EASF) (purified from embryo growth media of in vitro fertilized human ova). Hybridoma clones were produced by fusing their spleen cells with NS1 and P3X653 myeloma cell lines. The presence of specific anti-EASF monoclonal antibodies (mAb) in the hybridoma culture supernatants were tested by enzyme-linked immunosorbent assay. A total of 15 hybridoma clones were selected, and their products were purified and characterized. Each mAb bound specifically to its antigen in a dose-dependent manner. The affinity-purified EASF from embryo growth media demonstrated immunosuppressive activity on Concanavalin A-induced lymphocytes and the presence of 14 kDa, 24 kDa and 37 kDa factors. No such activity or similar molecules were identified when control growth media were analyzed. This clearly demonstrates that these mAb are indeed EASF-specific and are able to recognize biologically active immunosuppressive components in embryo growth media. These mAbs are presently being tested for the development of EASF-specific assay system.

Animals↗
PubMed1993

Inhibition of lipid A- and lipopolysaccharide-induced cytokine secretion, B cell mitogenesis, and lethal shock by lipid A-specific murine monoclonal antibodies.

Three murine hybridomas secreting IgM monoclonal antibodies (MAbs) to lipid A (LA) of Salmonella minnesota R595 were generated. These MAbs serologically cross-reacted with LA and lipopolysaccharide (LPS) of unrelated gram-negative bacterial species. All three MAbs significantly suppressed the ability of LA and LPS from various gram-negative bacteria to induce tumor necrosis factor (TNF)-alpha (36%-67%) and interleukin-1 (30%-98%) in murine peritoneal macrophages and to stimulate B lymphocytes (37%-78%). Lipid A-induced TNF alpha production was also suppressed in mice (86%-88%). All three antibodies protected adrenalectomized mice against lethal shock induced by LA of S. minnesota R595. Optimal protection was achieved with one of the antibodies (MLA-1), if it was administered 2 h before injection of lipid A, and full protection persisted < or = 24 h. Moreover, MLA-1 was able to protect adrenalized or D(+)-galactosamine-sensitized mice against lethal shock induced by LPS derived from various gram-negative bacteria. This cross-protection could be predicted on the basis of serologic cross-reactivity and cross-neutralization by MLA-1 of the bioactivity of the heterologous LA or LPS in vitro.

Animals↗