scholarly journals Relationship between chorionic gonadotropin immunomodulating effects and the initial functional activity of the splenocytes mediating the adoptive immune response

1993 ◽  
Vol 39 (1) ◽  
pp. 54-57 ◽  
Author(s):  
S. V. Shirshev ◽  
N. N. Kevorkov
Keyword(s):  
Immune Response ◽  
Chorionic Gonadotropin ◽  
Functional Activity ◽  
Low Dose ◽  
Interleukin 2 ◽  
Prostaglandin Synthesis ◽  
High Dose ◽  
Transfer System ◽  
Male Mice ◽  
Stimulation Of

CBA and (СВАхC57BL/6) F1 male mice were used in experiments. One hour incubation of splenocytes with chorionic gonadotropin in doses 10 or 50 MU/ml statistically significantly reduced the count of antibody-producing cells detectable in the syngeneic transfer system. Addition of conA or recombinant human interleukin 2 to the splenocyte culture did not alter the processes of the formation of antibodyproducing cells. Addition of chorionic gonadotropin simultaneously with conA resulted in discontinuation of the immunosuppression induced by a low hormone dose, whereas 50 MU/ml of chorionic gonadotropin in the presence of conA had a marked immunodepressant effect. Combination of interleukin 2 with chorionic gonadotropin lead either to immunosuppression cessation (10 MU/ml) or to more than twofold stimulation of the adoptive immune response (50 MU/ml). Voltaren a cycloxygenase inhibitor, was used in some experiments to elucidate the degree of endogenic prostaglandin relationships with the mechanisms of chorionic gonadotropin immunomodulating effects. Cycloxygenase activity was found to be related to the immunosuppressive effect of chorionic gonadotropin low dose, whereas the costimulating effect of a high dose of the hormone in the presence of interleukin 2 was unrelated to endogenic prostaglandin synthesis.

scholarly journals The effect of chorionic gonadotropin on the functional activity of some populations of splenocytes

1997 ◽  
Vol 43 (6) ◽  
pp. 40-42
Author(s):  
S. V. Shirshev
Keyword(s):  
Cell Culture ◽  
Chorionic Gonadotropin ◽  
Functional Activity ◽  
Low Dose ◽  
Active Oxygen ◽  
High Dose ◽  
Transfer System ◽  
A Cells ◽  
Nylon Fiber

Selective immunomodulating effects of high (50 IU/ml) and low (10 IU/ml) doses of chorionic gonadotropin (CG) on the functional activity of A cells and intact splenic T and В lymphocytes were revealed for the syngeneic transfer system. One- hour incubation of nonfractionated splenocytes with CG suppressed the formation of antibody-producing cells (APC) in le- thally irradiated syngeneic recipients. Removal of macrophages from the suspension of intact splenocytes arrested CG-induced immunosuppression and, in case of a low dose, activated the formation of APC. Addition of CG in a low dose to cell culture rich in В lymphocytes activated APC formation. A high dose of the hormone exerted no immunostimulating effect of this kind but selectively suppressed the function of T lymphocytes fractionated by fdtration through nylon fiber filters. Study of the functional activity of A cells by luminol-dependent chemiluminescence showed CG in the studied doses to suppress the generation of active oxygen forms, thus determining the key role of A cells as inducers of CG-dependent immunosuppression in a heterogeneous suspension of splenocytes.

scholarly journals Phase I Trial of Sequential Low-Dose 5-Aza-2′-Deoxycytidine Plus High-Dose Intravenous Bolus Interleukin-2 in Patients with Melanoma or Renal Cell Carcinoma

2006 ◽  
Vol 12 (15) ◽  
pp. 4619-4627 ◽  
Author(s):  
Jared A. Gollob ◽  
Catherine J. Sciambi ◽  
Bercedis L. Peterson ◽  
Tina Richmond ◽  
Monica Thoreson ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Phase I ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Phase I Trial ◽  
Low Dose ◽  
Interleukin 2 ◽  
High Dose ◽  
Intravenous Bolus

A phase II study of FolateImmune (EC90 with GP1–0100 adjuvant followed by EC17) with low dose cytokines interleukin-2 (IL-2) and interferon-α (IFN-α) in patients with refractory or metastatic cancer

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 13516-13516 ◽  
Author(s):  
R. Messmann ◽  
R. Amato ◽  
J. Hernandez-McClain ◽  
B. Conley ◽  
H. Rogers ◽  
...  
Keyword(s):  
Immune Response ◽  
Phase Ii ◽  
Low Dose ◽  
Metastatic Cancer ◽  
Cell Cancer ◽  
Interleukin 2 ◽  
Phase Ii Trials ◽  
Minor Response ◽  
Pathologic Classification ◽  
Study Laboratory

13516 Background: FolateImmune is a folate-receptor (FR)-targeted immunotherapy that induces an immune response against tumor cells by marking them with a folate-hapten conjugate. The conjugate is specifically designed to target FR, which is over-expressed in a variety of cancers. FolateImmune therapy is comprised of a vaccine fluorescein conjugate (EC90), an adjuvant (GP-0100), and a folate-hapten conjugate (EC17). Patients (pts) receive a series of subcutaneous (SQ) injections of EC90 vaccine to stimulate the production of antibodies to the fluorescein-hapten, followed by SQ injections of EC17, which forms a molecular bridge between the tumor cell and the endogenous circulating anti-fluorescein IgG antibody. This is thought to initiate an Fc-mediated immune response leading to antibody-dependent cellular cytotoxicity and/or phagocytosis. IL-2 and IFN are utilized at low doses (7 MIU and 3 MIU, respectively) to further promote an immune response. The Phase Ib objective is to determine the safety of EC90 vaccine/EC17 folate-targeted therapy in combination with IL-2 and IFN. The previous phase I trial explored the safety of FolateImmune without cytokines. Methods: This phase 1b safety study treated eligible patients with FolateImmune therapy at dose levels of 1.2 mg EC90 and EC17 of 0.3 mg/kg. Results: As of Jan 2, 2007, all patients have tolerated therapy without significant toxicity. Grade 1–2 toxicity included: chills, fever, and nausea. One patient has had a minor response and continues on study. Laboratory studies revealed decline in circulating FR+ cells. Of 6 pts enrolled, 5 had a pathologic classification of renal cell cancer (RCC). Conclusion: Preliminary data suggest that FolateImmune therapy, with the addition of low dose cytokines, may be administered in a safe and well-tolerated manner. Phase II trials are planned for RCC. No significant financial relationships to disclose.

Sympathetic and parasympathetic component of bradycardia triggered by stimulation of NTS P2X receptors

2006 ◽  
Vol 290 (2) ◽  
pp. H807-H812 ◽  
Author(s):  
Amy M. Kitchen ◽  
Donal S. O'Leary ◽  
Tadeusz J. Scislo
Keyword(s):  
Low Dose ◽  
Nucleus Tractus Solitarius ◽  
Receptor Activation ◽  
P2x Receptors ◽  
P2x Receptor ◽  
High Dose ◽  
Adrenergic Blockade ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Stimulation Of

We have previously shown that activation of P2X purinoceptors in the subpostremal nucleus tractus solitarius (NTS) produces a rapid bradycardia and hypotension. This bradycardia could occur via sympathetic withdrawal, parasympathetic activation, or a combination of both mechanisms. Thus we investigated the relative roles of parasympathetic activation and sympathetic withdrawal in mediating this bradycardia in chloralose-urethane anesthetized male Sprague-Dawley rats. Microinjections of the selective P2X purinoceptor agonist α,β-methylene ATP (25 pmol/50 nl and 100 pmol/50 nl) were made into the subpostremal NTS in control animals, after atenolol (2 mg/kg iv), a β1-selective antagonist, and after atropine methyl bromide (2 mg/kg iv), a muscarinic receptor antagonist. The bradycardia observed with activation of P2X receptors at the low dose of the agonist is mediated almost entirely by sympathetic withdrawal. After β1-adrenergic blockade, the bradycardia was reduced to just −5.1 ± 0.5 versus −28.8 ± 5.1 beats/min in intact animals. Muscarinic blockade did not produce any significant change in the bradycardic response at the low dose. At the high dose, both β1-adrenergic blockade and muscarinic blockade attenuated the bradycardia similarly, −37.4 ± 6.4 and −40.6 ± 3.7 beats/min, respectively, compared with −88.0 ± 11 beats/min in control animals. Double blockade of both β1-adrenergic and muscarinic receptors virtually abolished the response (−2.5 ± 0.8 beats/min). We conclude that the relative contributions of parasympathetic activation and sympathetic withdrawal are dependent on the extent of P2X receptor activation.

scholarly journals Impact of Low-Dose Occupational Exposure to Ionizing Radiation on T-Cell Populations and Subpopulations and Humoral Factors Included in the Immune Response

Dose-Response ◽  
2018 ◽  
Vol 16 (3) ◽  
pp. 155932581878556 ◽  
Author(s):  
Ilona Gyuleva ◽  
Jana Djounova ◽  
Ivanka Rupova
Keyword(s):  
Immune Response ◽  
T Cell ◽  
Occupational Exposure ◽  
Low Dose ◽  
Dose Range ◽  
Interleukin 2 ◽  
Cell Populations ◽  
Control Group ◽  
T Helper ◽  
Humoral Factors

The aim of the present study is to assess the effects of low-dose occupational exposure on T helper response. One Hundred five employees working in Nuclear Power Plant, Kozloduy, Bulgaria and control group of 32 persons are included in this investigation. Flow cytometry measurements of T-cell populations and subpopulations and natural killer T cells are performed and levels of G, A, and M immunoglobulins and interleukin 2 (IL-2), IL-4, and interferon γ were determined. The data interpreted with regard to cumulative doses, length of service, and age. The results of the present study are not enough to outline a clear impact of occupational radiation exposure on T helper populations. Nevertheless, the observed even slight trends in some lymphocyte’s populations and in cytokines profile give us the reason to assume a possibility of a gradual polarization of T helper 1 to T helper 2 immune response at dose range 100 to 200 mSv. The results of the present study indicate the need to perform a more detailed epidemiological survey including potential confounding and misclassifying factors and possible selection bias that could influence the results.

scholarly journals Mycobacterium tuberculosis in Chemokine Receptor 2-Deficient Mice: Influence of Dose on Disease Progression

2002 ◽  
Vol 70 (11) ◽  
pp. 5946-5954 ◽  
Author(s):  
Holly M. Scott ◽  
JoAnne L. Flynn
Keyword(s):  
Immune Response ◽  
Mycobacterium Tuberculosis ◽  
Cell Migration ◽  
Chemokine Receptor ◽  
Chemokine Receptors ◽  
Low Dose ◽  
High Dose ◽  
Long Term Effects ◽  
Spread Of Infection ◽  
Oxide Synthase

ABSTRACT Within a Mycobacterium tuberculosis-induced granuloma, lymphocytes and macrophages work together to control bacterial growth and limit the spread of infection. Chemokines and chemokine receptors are involved in cell migration and are logical candidates for a role in granuloma formation. In the present study we addressed the role of CC chemokine receptor 2 (CCR2) in M. tuberculosis infection. In previous studies (W. Peters et al., Proc. Natl. Acad. Sci. USA 98:7958-7963, 2001), CCR2−/− mice were found to be highly susceptible to a moderate or high dose of H37Rv administered intravenously (i.v.). We have expanded those studies to demonstrate that the susceptibility of CCR2−/− mice is dose dependent. After low-dose aerosol or i.v. infection of CCR2−/− mice with M. tuberculosis, there was a substantial delay in cell migration to the lungs and delayed expression of gamma interferon and inducible nitric oxide synthase. The CCR2−/− mice had a severe and prolonged deficiency in the number of macrophages in the lungs and an early increase in the number of neutrophils. Despite these deficiencies in cell migration, the CCR2−/− mice did not have increased bacterial loads in the lungs compared to wild-type (C57BL/6) mice and successfully formed granulomas. This finding is in contrast to CCR2−/− mice infected with a high dose of M. tuberculosis administered i.v. These results indicate that with low-dose infection, a delay in immune response in the lungs does not necessarily have detrimental long-term effects on the progression of the disease. The fact that CCR2−/− mice survive with substantially fewer macrophages in the low-dose models implies that the immune response to low-dose M. tuberculosis infection in mice is more robust than necessary to control the infection. Finally, these data demonstrate that, in cases of infectious disease in knockout models, clear phenotypes may not be evident when one is solely evaluating bacterial numbers and survival. Functional assays may be necessary to reveal roles for components of the multifactorial immune system.

scholarly journals Increased thromboxane mediates the adverse renal effects of interleukin-2 in rats.

1994 ◽  
Vol 4 (9) ◽  
pp. 1701-1710
Author(s):  
D Rubinger ◽  
E Cohen ◽  
Y Haviv ◽  
J Bernheim ◽  
E Shiloni ◽  
...  
Keyword(s):  
Body Weight ◽  
Urinary Excretion ◽  
Low Dose ◽  
Combined Therapy ◽  
Interleukin 2 ◽  
Chronic Administration ◽  
Urinary Sodium Excretion ◽  
Metabolic Effects ◽  
High Dose ◽  
Sodium And Potassium

The capillary leak syndrome with decreased GFR and renal water and sodium retention after recombinant interleukin-2 (IL-2) administration may arise from endothelial activation via an increase in prostaglandin synthesis. This study was undertaken to better define the role of the prostaglandin system in the renal and metabolic effects of IL-2 administration in rats. The chronic administration of IL-2 (100,000 U/kg, thrice daily, ip) resulted in a significant increase in body weight, a decrease in GFR and in the urinary excretion of sodium and potassium, and an increase in the urinary excretion of thromboxane (TXB2). After combined IL-2 and low-dose indomethacin (1.7 mg/kg per day po), a significant decrease in body weight with normalization of GFR, of the urinary excretion of Na, and of urinary TXB2 was noted in animals receiving combined therapy as compared with those receiving IL-2 alone. In contrast, high-dose indomethacin administration (33.3 mg/kg po for the last 3 days of the study) was associated with a further decrease in GFR, enhancement of the sodium and potassium retention, and suppression of prostaglandin E2 excretion. The administration of the thromboxane receptor antagonist SQ 29548 in IL-2-treated rats led to a reversal of the fall in GFR induced by the lymphokine without significant changes in urinary sodium excretion. These results support the hypothesis that thromboxane is an important mediator of the renal and systemic effects of IL-2. These effects are reversed at least partly by low-dose indomethacin, which selectively suppresses thromboxane A2 (TXA2) synthesis, or by TXA2 receptor antagonism.

Stimulation of folliculogenesis with low-dose human chorionic gonadotropin (hCG) alone in ovulation induction

2004 ◽  
Vol 82 ◽  
pp. S3 ◽  
Author(s):  
M. Filicori ◽  
G.E. Cognigni ◽  
L. Parmegiani ◽  
S. Taraborrelli ◽  
E. Gamberini ◽  
...  
Keyword(s):  
Chorionic Gonadotropin ◽  
Human Chorionic Gonadotropin ◽  
Ovulation Induction ◽  
Low Dose ◽  
Stimulation Of
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