Erythropoietin and Cyclophosphamide Combined Treatment Additively Enhances Immunoglobulin Production in Mice

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 4913-4913
Author(s):  
Lilach Lifshitz ◽  
Assaf Berger ◽  
Maayan Avneon ◽  
Moshe Mittelman ◽  
Drorit Neumann
Keyword(s):  
Humoral Immunity ◽  
Combined Treatment ◽  
Humoral Response ◽  
Serum Levels ◽  
Immunosuppressive Agent ◽  
Immunoglobulin Production ◽  
Humoral Immune ◽  
C57bl Mice ◽  
High Doses ◽  
Cancer Related Anemia

Abstract Erythropoietin (EPO) is an important component in the treatment of cancer patients for improvement of cancer related anemia. EPO treatment for cancer related anemia is usually combined with chemotherapy. Cyclophosphamide (CP) is a known cytotoxic alkylating agent widely used in cancer chemotherapy. While at high doses it functions as an immunosuppressive agent, the anti-neoplastic activities of CP at low doses are attributed to enhancement of cellular and humoral immunity e.g. (Berd et al., Cancer Res; 1984). We have previously shown that EPO displays anti-neoplastic activities (Mittelman, 2001, 2004) and that EPO treatment is associated with enhancement of both the humoral and cellular immune responses (Prutchi-Sagiv 2006, Katz 2007). Here we focused on a murine model of DNP-KLH-injection, used to assess the humoral response in mice. Recently we demonstrated that administration of high doses of EPO (180U×3) to DNP-KLH-injected C57BL mice resulted in an increase in anti-DNP immunoglobulin G1 (IgG1) production. The present study was designed to examine the effect of combining low dose CP (12.5mg/kg ×2) used to achieve an anti-neoplastic activity, with a lower dose of recombinant human EPO (rHuEPO; 90U×3) on the humoral immune response of the DNP-KLH-injected mice, thus simulating the conditions of patient care. Hence, we compared anti-DNP Ig serum levels in DNP-KLH-injected C57BL mice that were treated with either EPO or CP alone, or the combination of CP and EPO (CP-EPO). CP treatment alone resulted in increased levels of serum anti-DNP IgG1 (O.D.(CP) = 0.38±0.06 vs O.D.(Non treated) = 0.18±0.064). In contrast, EPO treatment alone enhanced serum levels of IgG2 (O.D.(EPO) = 0.47±0.09 vs O.D.(Non treated) = 0.18±0.069). CP or EPO alone did not affect the total levels of anti-DNP total Ig (O.D.(EPO) = 0.37±0.07 vs O.D.(Non treated) = 0.28±0.04). Yet, the combined CP-EPO treatment resulted in increased levels of anti-DNP total Ig (O.D.(EPO+CP) = 0.48±0.05 vs O.D.(EPO or CP) = 0.37±0.04), maintaining the higher levels of IgG1 (O.D.(EPO+CP) = 0.38±0.06) and IgG2 (O.D.(EPO+CP) = 0.49±0.1). In summary, the combined CP-EPO treatment additively improved immunoglobulin production, compared to treatment with CP or EPO alone. We thus demonstrate that in context of chemotherapy treatment as usually administered in the clinic, EPO can enhance humoral immunity alongside its erythropoietic activities. Our findings emphasize the role of EPO as an immunomodulator, particularly when given as treatment in a combined therapeutic panel

scholarly journals Characterization of the significant decline in humoral immune response six months post-SARS-CoV-2 mRNA vaccination: A systematic review

2021 ◽  
Author(s):  
Kin Israel Notarte ◽  
Israel Guerrero-Arguero ◽  
Jacqueline Veronica Velasco ◽  
Abbygail Therese Ver ◽  
Maria Helena Santos de Oliveira ◽  
...  
Keyword(s):  
Humoral Response ◽  
Serum Levels ◽  
Related Factors ◽  
Post Vaccination ◽  
Humoral Immune ◽  
Antibody Titers ◽  
Waning Immunity ◽  
Antibody Class ◽  
Antibody Decline ◽  
Primary Cycle

Accumulating evidence shows a progressive decline in the efficacy of coronavirus disease 2019 (COVID-19) mRNA vaccines such as Pfizer-BioNTech (mRNA BNT161b2) and Moderna (mRNA-1273) in preventing breakthrough infections due to diminishing humoral immunity over time. Thus, this review characterizes the kinetics of anti-SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2) antibodies after the second dose of a primary cycle of COVID-19 mRNA vaccination. A systematic search of literature was performed and a total of 18 studies (N=15,980) were identified and reviewed. The percent difference of means of reported antibody titers were then calculated to determine the decline in humoral response after the peak levels post-vaccination. Findings revealed that the peak humoral response was reached at 21-28 days after the second dose, after which serum levels progressively diminished at 4-6 months post-vaccination. Additionally, results showed that regardless of age, sex, serostatus and presence of comorbidities, longitudinal data reporting antibody measurement exhibited a decline of both anti-receptor binding domain (RBD) IgG and anti-spike IgG, ranging from 94-95% at 90-180 days and 55-85% at 140-160 days, respectively, after the peak antibody response. This suggests that the rate of antibody decline may be independent of patient-related factors and peak antibody titers but mainly a function of time and antibody class/molecular target. Hence, this study highlights the necessity of more efficient vaccination strategies to provide booster administration in attenuating the effects of waning immunity, especially in the appearance of new variants of concerns (VoCs).

Effects of estrogen and growth hormone on skeleton in the ovariectomized rat with hypophysectomy

1997 ◽  
Vol 273 (4) ◽  
pp. E734-E742 ◽  
Author(s):  
James K. Yeh ◽  
Meng-Meng Chen ◽  
John F. Aloia
Keyword(s):  
Growth Hormone ◽  
Bone Formation ◽  
Cancellous Bone ◽  
Bone Growth ◽  
Combined Treatment ◽  
Serum Levels ◽  
Hormone Deficiency ◽  
High Dose ◽  
Sprague Dawley ◽  
High Doses

To investigate whether growth hormone (GH) and 17β-estradiol (E2) replacement can prevent osteopenia induced by pituitary and ovarian hormone deficiency [by hypophysectomy and ovariectomy (HX+OV)], we administered relatively low doses of GH (2.3 IU ⋅ kg−1 ⋅ day−1) and E2 (100 μg ⋅ kg−1 ⋅ wk−1) in experiment 1 and relatively high doses of GH (13.5 IU ⋅ kg−1 ⋅ day−1) and E2 (3,500 μg ⋅ kg−1 ⋅ wk−1) in experiment 2 to 2-mo-old HX+OV Sprague-Dawley rats for 6 wk. Our data show that the HX+OV of rats results in diminished periosteal bone formation, longitudinal bone growth, and decreased cancellous bone volume. Administration of either the low or high dose of GH to these rats increased their systemic growth, serum levels of osteocalcin, and cortical bone formation. Either low or high doses of GH or E2 alone only partially prevent cancellous bone loss. However, the combined treatment of GH plus E2 resulted in an additive increase in the cancellous bone mass. We conclude that the additive effect of GH plus E2 on cancellous bone is attributed to the suppressive effect of E2 on bone resorption and the anabolic effect of GH on bone formation.

Humoral Immunity in Heart Failure

2019 ◽  
Vol 19 (1) ◽  
pp. 14-18 ◽  
Author(s):  
Amrita Sarkar ◽  
Khadija Rafiq
Keyword(s):  
Heart Failure ◽  
Humoral Immunity ◽  
Treatment Strategies ◽  
Pathophysiological Mechanism ◽  
Peripheral Vascular ◽  
Cardiac Inflammation ◽  
Humoral Immune ◽  
Humoral Immune System ◽  
New Treatment ◽  
Immunity Function

Cardiovascular Disease (CVD) is a class of diseases that involve disorders of heart and blood vessels, including hypertension, coronary heart disease, cerebrovascular disease, peripheral vascular disease, which finally lead to Heart Failure (HF). There are several treatments available all over the world, but still, CVD and heart failure became the number one problem causing death every year worldwide. Both experimental and clinical studies have shown a role for inflammation in the pathogenesis of heart failure. This seems related to an imbalance between pro-inflammatory and anti-inflammatory cytokines. Cardiac inflammation is a major pathophysiological mechanism operating in the failing heart, regardless of HF aetiology. Disturbances of the cellular and humoral immune system are frequently observed in heart failure. This review describes how B-cells play a specific role in the heart failure states. There is an urgent need to identify novel therapeutic targets and develop advanced therapeutic strategies to combat the syndrome of HF. Understanding and describing the elements of the humoral immunity function are essential and may suggest potential new treatment strategies.

High doses of antipsychotic polypharmacy are related to an increase in serum levels of pentosidine in patients with schizophrenia

2017 ◽  
Vol 76 ◽  
pp. 42-48 ◽  
Author(s):  
Takahiro Sannohe ◽  
Tohru Ohnuma ◽  
Masayoshi Takeuchi ◽  
Eriko Tani ◽  
Yasue Miki ◽  
...  
Keyword(s):  
Serum Levels ◽  
High Doses

scholarly journals Titers of Neutralizing Antibodies against SARS-CoV-2 Are Independent of Symptoms of Non-Severe COVID-19 in Young Adults

Viruses ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 284
Author(s):  
Hulda R. Jonsdottir ◽  
Michel Bielecki ◽  
Denise Siegrist ◽  
Thomas W. Buehrer ◽  
Roland Züst ◽  
...  
Keyword(s):  
Young Adults ◽  
Neutralizing Antibodies ◽  
Severe Disease ◽  
Humoral Response ◽  
Neutralizing Antibody ◽  
Neutralization Assay ◽  
Asymptomatic Infection ◽  
Homogeneous Population ◽  
Humoral Immune ◽  
Antibody Titers

Neutralizing antibodies are an important part of the humoral immune response to SARS-CoV-2. It is currently unclear to what extent such antibodies are produced after non-severe disease or asymptomatic infection. We studied a cluster of SARS-CoV-2 infections among a homogeneous population of 332 predominantly male Swiss soldiers and determined the neutralizing antibody response with a serum neutralization assay using a recombinant SARS-CoV-2-GFP. All patients with non-severe COVID-19 showed a swift humoral response within two weeks after the onset of symptoms, which remained stable for the duration of the study. One month after the outbreak, titers in COVID-19 convalescents did not differ from the titers of asymptomatically infected individuals. Furthermore, symptoms of COVID-19 did not correlate with neutralizing antibody titers. Therefore, we conclude that asymptomatic infection can induce the same humoral immunity as non-severe COVID-19 in young adults.

TLR4 regulates rabies virus-induced humoral immunity through recruitment of cDC2 to lymph organs

2021 ◽  
Author(s):  
Chen Chen ◽  
Chengguang Zhang ◽  
Haoqi Li ◽  
Zongmei Wang ◽  
Yueming Yuan ◽  
...  
Keyword(s):  
Immune Response ◽  
Immune Responses ◽  
Rabies Virus ◽  
Humoral Immunity ◽  
Humoral Immune Response ◽  
Critical Role ◽  
Wild Type ◽  
Humoral Immune ◽  
Specific Igg ◽  
Molecular Patterns

Rabies, caused by rabies virus (RABV), is fatal to both humans and animals around the world. Effective clinical therapy for rabies has not been achieved, and vaccination is the most effective means of preventing and controlling rabies. Although different vaccines, such as live attenuated and inactivated vaccines, can induce different immune responses, different expression of pattern recognition receptors (PRRs) also causes diverse immune responses. Toll-like receptor 4 (TLR4) is a pivotal PRR that induces cytokine production and bridges innate and adaptive immunity. Importantly, TLR4 recognizes various virus-derived pathogen-associated molecular patterns (PAMPs) and virus-induced damage-associated molecular patterns (DAMPs), usually leading to the activation of immune cells. However, the role of TLR4 in the humoral immune response induced by RABV has not been revealed yet. Based on TLR4-deficient ( TLR4 -/- ) and wild-type (WT) mouse models, we report that TLR4-dependent recruitment of the conventional type-2 dendritic cells (CD8α - CD11b + cDC2) into secondary lymph organs (SLOs) is critical for antigen presentation. cDC2-initiated differentiation of Tfh cells promotes the proliferation of germinal centre (GC) B cells, the formation of GCs, and the production of plasma cells (PCs), all of which contribute to the production of RABV-specific IgG and virus-neutralizing antibodies (VNAs). Collectively, our work demonstrates that TLR4 is necessary for the recruitment of cDC2 and for the induction of RABV-induced humoral immunity, which is regulated by the cDC2-Tfh-GC B axis. IMPORTANCE Vaccination is the most efficient method to prevent rabies. TLR4, a well-known immune sensor, plays a critical role in initiating innate immune response. Here, we found that TLR4 deficiency ( TLR4 -/- ) mice suppressed the induction of humoral immune response after immunization with rabies virus (RABV), including reduced production of VNAs and RABV-specific IgG, compared with that occurred in wild-type (WT) mice. As a consequence, TLR4 -/- mice exhibited higher mortality than WT mice after challenge with virulent RABV. Importantly, further investigation found that TLR4 signaling promoted the recruitment of cDC2 (CD8α + CD11b - ), a subset of cDCs known to induce CD4 + T cell immunity through their MHC-II presentation machinery. Our results imply that TLR4 is indispensable for an efficient humoral response to rabies vaccine, which provides new insight into the development of novel rabies vaccines.

scholarly journals mRNA vaccination in people over 80 years of age induces strong humoral immune responses against SARS-CoV-2 with cross neutralization of P.1 Brazilian variant

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Helen Parry ◽  
Gokhan Tut ◽  
Rachel Bruton ◽  
Sian Faustini ◽  
Christine Stephens ◽  
...  
Keyword(s):  
Immune Responses ◽  
Cellular Response ◽  
Humoral Response ◽  
Antibody Responses ◽  
Vaccine Platform ◽  
Humoral Immune ◽  
Vaccine Responses ◽  
Cellular Immune Responses ◽  
Humoral Immune Responses ◽  
Cellular Immune

Age is the major risk factor for mortality after SARS-CoV-2 infection and older people have received priority consideration for COVID-19 vaccination. However, vaccine responses are often suboptimal in this age group and few people over the age of 80 years were included in vaccine registration trials. We determined the serological and cellular response to spike protein in 100 people aged 80–96 years at 2 weeks after the second vaccination with the Pfizer BNT162b2 mRNA vaccine. Antibody responses were seen in every donor with high titers in 98%. Spike-specific cellular immune responses were detectable in only 63% and correlated with humoral response. Previous SARS-CoV-2 infection substantially increased antibody responses after one vaccine and antibody and cellular responses remained 28-fold and 3-fold higher, respectively, after dual vaccination. Post-vaccine sera mediated strong neutralization of live Victoria infection and although neutralization titers were reduced 14-fold against the P.1 variant first discovered in Brazil they remained largely effective. These data demonstrate that the mRNA vaccine platform delivers strong humoral immunity in people up to 96 years of age and retains broad efficacy against the P.1 variant of concern.

scholarly journals Dynamics of humoral immune response in pregnant mares and foals vaccinated with Theileria equi recombinant EMA-2

2018 ◽  
Vol 38 (6) ◽  
pp. 1105-1109
Author(s):  
Alice C. Santos ◽  
Fábio P.L. Leite ◽  
Ana M. Vianna ◽  
Guilherme B. Weege ◽  
Ilusca S. Finger ◽  
...  
Keyword(s):  
Immune Response ◽  
Humoral Immune Response ◽  
Fold Increase ◽  
Serum Levels ◽  
Vaccination Schedule ◽  
Theileria Equi ◽  
Humoral Immune ◽  
Baseline Values ◽  
Antibody Levels ◽  
First Time

ABSTRACT: Theileria equi is an infectious hemoprotozoan agent of equine piroplasmosis, a disease that has severe economic and sanitary impact internationally. In addition to its common clinical features, piroplasmosis can cause gestational losses and neonatal damage, which makes neonates susceptible to this disease. The aim of this study was to evaluate the dynamics of humoral immune response to recombinant EMA-2 of T. equi in pregnant mares and foals, as well as the transfer of vaccine antibodies through the colostrum ingested by sucking foals. For vaccine production, the EMA-2 expression gene was cloned and expressed in the yeast species, Pichia pastoris. Thirty-six horses were used, of which 18 were pregnant mares and 18 were foals. The mares were divided into control and vaccinated groups, and the vaccinated group received three doses of rEMA-2 every 21 days starting at 300 days of gestation. Foals from vaccinated and control groups were evaluated until the sixth month of life. The production of antibodies by foals on the rEMA-2 vaccination schedule was also evaluated from the second month of life. Foals in the vaccinated group had received three doses of the vaccine every 21 days. The method used to evaluate serum and colostrum samples was indirect ELISA, and plates were sensitized with the rEMA-2 protein. At the end of the vaccination schedule, vaccinated mares showed a 2.3-fold increase in antibody levels when compared to baseline values. The colostrum of vaccinated mares presented antibody levels of 1.0432±0.33. Foals delivered by vaccinated mares presented levels of antibodies greater than those of foals delivered by control mares after their first time sucking (at about twelve hours after birth). Foals vaccinated in the second month of life showed an 8.3-fold increase in antibody levels when compared to baseline values. The vaccination schedule with rEMA-2 was able to stimulate humoral immunity in pregnant mares. Vaccine immunoglobins were concentrated in the colostrum of vaccinated mares and foals delivered by these mares showed an increase in serum levels of vaccine antibodies after the first-time sucking.

scholarly journals Impact of Binge Alcohol Intoxication on the Humoral Immune Response during Burkholderia spp. Infections

2019 ◽  
Vol 7 (5) ◽  
pp. 125
Author(s):  
Ryan M. Moreno ◽  
Victor Jimenez ◽  
Fernando P. Monroy
Keyword(s):  
Immune Response ◽  
Humoral Immune Response ◽  
Opportunistic Infections ◽  
Alcohol Intoxication ◽  
Experimental Studies ◽  
Adaptive Immune System ◽  
Humoral Response ◽  
Humoral Immune ◽  
Healthy Humans ◽  
The Impact

Burkholderia pseudomallei, the causative agent of melioidosis can occur in healthy humans, yet binge alcohol use is progressively being recognized as a major risk factor. Currently, no experimental studies have investigated the effects of binge alcohol on the adaptive immune system during an active infection. In this study, we used B. thailandensis and B. vietnamiensis, to investigate the impact of a single binge alcohol episode on the humoral response during infection. Eight-week-old female C57BL/6 mice were administered alcohol comparable to human binge drinking (4.4 g/kg) or PBS intraperitoneally 30 min before intranasal infection. Mice infected with B. thailandensis had a 100% survival rate, while those infected with B. vietnamiensis had a 33% survivability rate when a binge alcohol dose was administered. B. thailandensis was detected in blood of mice administered alcohol at only 7 days post infection (PI), while those infected with B. vietnamiensis and receiving alcohol were found throughout the 28-day infection as well as in tissues at day 28 PI. Binge alcohol elevated IgM and delayed IgG specific to the whole cell lysate (WCL) of B. vietnamiensis but not B. thailandensis infections. Differences in immunogenicity of B. pseudomallei near-neighbors provide a framework for novel insights into the effects of binge alcohol’s suppression of the humoral immune response that can cause opportunistic infections in otherwise healthy hosts.

scholarly journals Anti–4-1bb Monoclonal Antibodies Abrogate T Cell–Dependent Humoral Immune Responses in Vivo through the Induction of Helper T Cell Anergy

1999 ◽  
Vol 190 (10) ◽  
pp. 1535-1540 ◽  
Author(s):  
Robert S. Mittler ◽  
Tina S. Bailey ◽  
Kerry Klussman ◽  
Mark D. Trailsmith ◽  
Michael K. Hoffmann
Keyword(s):  
Immune Response ◽  
T Cells ◽  
Monoclonal Antibodies ◽  
T Cell ◽  
B Cells ◽  
Humoral Immunity ◽  
Cd8 T Cells ◽  
Immunodeficient Mice ◽  
Humoral Immune

The 4-1BB receptor (CDw137), a member of the tumor necrosis factor receptor superfamily, has been shown to costimulate the activation of T cells. Here we show that anti–mouse 4-1BB monoclonal antibodies (mAbs) inhibit thymus-dependent antibody production by B cells. Injection of anti–4-1BB mAbs into mice being immunized with cellular or soluble protein antigens induced long-term anergy of antigen-specific T cells. The immune response to the type II T cell–independent antigen trinintrophenol-conjugated Ficoll, however, was not suppressed. Inhibition of humoral immunity occurred only when anti–4-1BB mAb was given within 1 wk after immunization. Anti–4-1BB inhibition was observed in mice lacking functional CD8+ T cells, indicating that CD8+ T cells were not required for the induction of anergy. Analysis of the requirements for the anti–4-1BB–mediated inhibition of humoral immunity revealed that suppression could not be adoptively transferred with T cells from anti–4-1BB–treated mice. Transfer of BALB/c splenic T cells from sheep red blood cell (SRBC)-immunized and anti–4-1BB–treated mice together with normal BALB/c B cells into C.B-17 severe combined immunodeficient mice failed to generate an anti-SRBC response. However, B cells from the SRBC-immunized, anti–4-1BB–treated BALB/c mice, together with normal naive T cells, exhibited a normal humoral immune response against SRBC after transfer, demonstrating that SRBC-specific B cells were left unaffected by anti–4-1BB mAbs.

Sign in / Sign up

Export Citation Format

Share Document