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1.
J Clin Immunol ; 44(7): 163, 2024 Jul 15.
Article in English | MEDLINE | ID: mdl-39008214

ABSTRACT

BACKGROUND: Cryptococcosis is a life-threatening disease caused by Cryptococcus neoformans or C. gattii. Neutralizing autoantibodies (auto-Abs) against granulocyte-macrophage colony-stimulating factor (GM-CSF) in otherwise healthy adults with cryptococcal meningitis have been described since 2013. We searched for neutralizing auto-Abs in sera collected from Colombian patients with non-HIV-associated cryptococcosis in a retrospective national cohort from 1997 to 2016. METHODS: We reviewed clinical and laboratory records and assessed the presence of neutralizing auto-Abs against GM-CSF in 30 HIV negative adults with cryptococcosis (13 caused by C. gattii and 17 caused by C. neoformans). RESULTS: We detected neutralizing auto-Abs against GM-CSF in the sera of 10 out of 13 (77%) patients infected with C. gattii and one out of 17 (6%) patients infected with C. neoformans. CONCLUSIONS: We report eleven Colombian patients diagnosed with cryptococcosis who had auto-Abs that neutralize GM-CSF. Among these patients, ten were infected with C. gattii and only one with C. neoformans.


Subject(s)
Antibodies, Neutralizing , Autoantibodies , Cryptococcosis , Cryptococcus gattii , Cryptococcus neoformans , Granulocyte-Macrophage Colony-Stimulating Factor , Humans , Granulocyte-Macrophage Colony-Stimulating Factor/immunology , Autoantibodies/blood , Autoantibodies/immunology , Male , Colombia , Female , Adult , Cryptococcus gattii/immunology , Middle Aged , Cryptococcus neoformans/immunology , Cryptococcosis/immunology , Cryptococcosis/diagnosis , Antibodies, Neutralizing/blood , Antibodies, Neutralizing/immunology , Retrospective Studies , HIV Seronegativity/immunology , Young Adult , Aged
2.
Stem Cell Res Ther ; 15(1): 208, 2024 Jul 11.
Article in English | MEDLINE | ID: mdl-38992782

ABSTRACT

BACKGROUND: Mesenchymal stromal cells (MSCs) tropism for tumours allows their use as carriers of antitumoural factors and in vitro transcribed mRNA (IVT mRNA) is a promising tool for effective transient expression without insertional mutagenesis risk. Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a cytokine with antitumor properties by stimulating the specific immune response. The aim of this work was to generate modified MSCs by IVT mRNA transfection to overexpress GM-CSF and determine their therapeutic effect alone or in combination with doxorubicin (Dox) in a murine model of hepatocellular carcinoma (HCC). METHODS: DsRed or GM-CSF IVT mRNAs were generated from a cDNA template designed with specific primers followed by reverse transcription. Lipofectamine was used to transfect MSCs with DsRed (MSC/DsRed) or GM-CSF IVT mRNA (MSC/GM-CSF). Gene expression and cell surface markers were determined by flow cytometry. GM-CSF secretion was determined by ELISA. For in vitro experiments, the J774 macrophage line and bone marrow monocytes from mice were used to test GM-CSF function. An HCC model was developed by subcutaneous inoculation (s.c.) of Hepa129 cells into C3H/HeN mice. After s.c. injection of MSC/GM-CSF, Dox, or their combination, tumour size and mouse survival were evaluated. Tumour samples were collected for mRNA analysis and flow cytometry. RESULTS: DsRed expression by MSCs was observed from 2 h to 15 days after IVT mRNA transfection. Tumour growth remained unaltered after the administration of DsRed-expressing MSCs in a murine model of HCC and MSCs expressing GM-CSF maintained their phenotypic characteristic and migration capability. GM-CSF secreted by modified MSCs induced the differentiation of murine monocytes to dendritic cells and promoted a proinflammatory phenotype in the J774 macrophage cell line. In vivo, MSC/GM-CSF in combination with Dox strongly reduced HCC tumour growth in C3H/HeN mice and extended mouse survival in comparison with individual treatments. In addition, the tumours in the MSC/GM-CSF + Dox treated group exhibited elevated expression of proinflammatory genes and increased infiltration of CD8 + T cells and macrophages. CONCLUSIONS: Our results showed that IVT mRNA transfection is a suitable strategy for obtaining modified MSCs for therapeutic purposes. MSC/GM-CSF in combination with low doses of Dox led to a synergistic effect by increasing the proinflammatory tumour microenvironment, enhancing the antitumoural response in HCC.


Subject(s)
Carcinoma, Hepatocellular , Doxorubicin , Granulocyte-Macrophage Colony-Stimulating Factor , Liver Neoplasms , Mesenchymal Stem Cells , RNA, Messenger , Animals , Carcinoma, Hepatocellular/therapy , Carcinoma, Hepatocellular/pathology , Carcinoma, Hepatocellular/genetics , Mesenchymal Stem Cells/metabolism , Mice , Liver Neoplasms/therapy , Liver Neoplasms/pathology , Liver Neoplasms/genetics , RNA, Messenger/metabolism , RNA, Messenger/genetics , Doxorubicin/pharmacology , Doxorubicin/therapeutic use , Granulocyte-Macrophage Colony-Stimulating Factor/genetics , Granulocyte-Macrophage Colony-Stimulating Factor/metabolism , Cell Line, Tumor , Mesenchymal Stem Cell Transplantation/methods , Humans , Mice, Inbred C3H , Transfection
3.
Res Sq ; 2024 Jan 19.
Article in English | MEDLINE | ID: mdl-38313298

ABSTRACT

Background: Cryptococcosis is a life-threatening disease caused by Cryptococcus neoformans or C. gattii. Autoantibodies (auto-Abs) neutralizing granulocyte-macrophage colony-stimulating factor (GM-CSF) in otherwise healthy adults with cryptococcal meningitis have been described since 2013. We searched for neutralizing auto-Abs in sera from Colombian patients with non-HIV related cryptococcosis in a retrospective national cohort collected from 1997 to 2016. Methods: We reviewed clinical and laboratory records and assessed the presence of neutralizing auto-Abs in 30 HIV (-) adults presenting cryptococcosis (13 by C. gattii, and 17 by C. neoformans). Results: We detected auto-Abs neutralizing GM-CSF in the plasma of 9 out of 13 (69%) patients infected with C. gattii and 1 out of 17 (6%) patients with C. neoformans. Conclusions: We report ten Colombian patients with cryptococcosis due to auto-Abs neutralizing GM-CSF. Nine of the ten patients were infected with C. gattii, and only one with C. neoformans.

4.
Cytokine ; 173: 156417, 2024 01.
Article in English | MEDLINE | ID: mdl-37944421

ABSTRACT

Colony-stimulating factors (CSFs) are key cytokines responsible for the production, maturation, and mobilization of the granulocytic and macrophage lineages from the bone marrow, which have been gaining attention for playing pro- and/or anti-tumorigenic roles in cancer. Head and neck cancers (HNCs) represent a group of heterogeneous neoplasms with high morbidity and mortality worldwide. Treatment for HNCs is still limited even with the advancements in cancer immunotherapy. Novel treatments for patients with recurrent and metastatic HNCs are urgently needed. This article provides an in-depth review of the role of hematopoietic cytokines such as granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage colony-stimulating factor (GM-CSF), macrophage colony-stimulating factor (M-CSF), and interleukin-3 (IL-3; also known as multi-CSF) in the HNCs tumor microenvironment. We have reviewed current results from clinical trials using CSFs as adjuvant therapy to treat HNCs patients, and also clinical findings reported to date on the therapeutic application of CSFs toxicities arising from chemoradiotherapy.


Subject(s)
Colony-Stimulating Factors , Head and Neck Neoplasms , Humans , Interleukin-3 , Granulocyte Colony-Stimulating Factor/therapeutic use , Cytokines , Granulocytes , Head and Neck Neoplasms/drug therapy , Tumor Microenvironment
5.
Physiol Rep ; 11(23): e15861, 2023 Dec.
Article in English | MEDLINE | ID: mdl-38086735

ABSTRACT

Pulmonary mechanics has been traditionally viewed as determined by lung size and physical factors such as frictional forces and tissue viscoelastic properties, but few information exists regarding potential influences of cytokines and hormones on lung function. Concentrations of 28 cytokines and hormones were measured in saliva from clinically healthy scholar children, purposely selected to include a wide range of body mass index (BMI). Lung function was assessed by impulse oscillometry, spirometry, and diffusing capacity for carbon monoxide, and expressed as z-score or percent predicted. Ninety-six scholar children (55.2% female) were enrolled. Bivariate analysis showed that almost all lung function variables correlated with one or more cytokine or hormone, mainly in boys, but only some of them remained statistically significant in the multiple regression analyses. Thus, after adjusting by height, age, and BMI, salivary concentrations of granulocyte-macrophage colony-stimulating factor (GM-CSF) in boys were associated with zR5-R20 and reactance parameters (zX20, zFres, and zAX), while glucagon inversely correlated with resistances (zR5 and zR20). Thus, in physiological conditions, part of the mechanics of breathing might be influenced by some cytokines and hormones, including glucagon and GM-CSF. This endogenous influence is a novel concept that warrants in-depth characterization.


Subject(s)
Cytokines , Granulocyte-Macrophage Colony-Stimulating Factor , Male , Child , Humans , Female , Cross-Sectional Studies , Glucagon , Lung
6.
J Clin Immunol ; 43(5): 921-932, 2023 07.
Article in English | MEDLINE | ID: mdl-36821021

ABSTRACT

BACKGROUND: Cryptococcosis is a potentially life-threatening fungal disease caused by encapsulated yeasts of the genus Cryptococcus, mostly C. neoformans or C. gattii. Cryptococcal meningitis is the most frequent clinical manifestation in humans. Neutralizing autoantibodies (auto-Abs) against granulocyte-macrophage colony-stimulating factor (GM-CSF) have recently been discovered in otherwise healthy adult patients with cryptococcal meningitis, mostly caused by C. gattii. We hypothesized that three Colombian patients with cryptococcal meningitis caused by C. neoformans in two of them would carry high plasma levels of neutralizing auto-Abs against GM-CSF. METHODS: We reviewed medical and laboratory records, performed immunological evaluations, and tested for anti-cytokine auto-Abs three previously healthy HIV-negative adults with disseminated cryptococcosis. RESULTS: Peripheral blood leukocyte subset levels and serum immunoglobulin concentrations were within the normal ranges. We detected high levels of neutralizing auto-Abs against GM-CSF in the plasma of all three patients. CONCLUSIONS: We report three Colombian patients with disseminated cryptococcosis associated with neutralizing auto-Abs against GM-CSF. Further studies should evaluate the genetic contribution to anti-GM-CSF autoantibody production and the role of the GM-CSF signaling pathway in the immune response to Cryptococcus spp.


Subject(s)
Cryptococcosis , Cryptococcus neoformans , Meningitis, Cryptococcal , Adult , Humans , Granulocyte-Macrophage Colony-Stimulating Factor , Meningitis, Cryptococcal/diagnosis , Autoantibodies , Colombia , Cryptococcosis/diagnosis
7.
Rev. bras. ginecol. obstet ; Rev. bras. ginecol. obstet;44(11): 1047-1051, Nov. 2022. tab, graf
Article in English | LILACS | ID: biblio-1423277

ABSTRACT

Abstract Objective The use of granulocyte macrophage colony-stimulating factor (GM-CSF)-containing medium, which is a commercial medium that is used for cultivation of embryos in in vitro fertilization (IVF) treatments, has been suggested to increase the efficiency of this procedure in patients with previous multiple unsuccessful attempts. In this retrospective study, we analyzed GM-CSF-containing embryo culture media compared with traditional culture media in terms of development of embryos, pregnancy, and ongoing pregnancy success and live birth rates. Methods This is a prospective case control study conducted in a single center. A total of 131 unexplained infertility patients were included in the study. A cohort of 69 patients whose embryos were cultured in GM-CSF-containing medium and a control group of 62 age-matched patients whose embryos were cultured in conventional Sage One Step medium were included in the study. The major study outcomes were achievement of pregnancy and ongoing pregnancy rate at 12 weeks of gestation. Results The pregnancy and ongoing pregnancy rates of the patients whose embryos were cultured in GM-CSF-containing medium were 39.13% and 36.23%, respectively. These were higher than the rates of the control group, which were 30.65% and 29.03%, respectively, although this difference was not statistically significant. In addition, the 5th-day embryo transfer percentage in the GM-CSF group was higher than in the control group (34.78% versus 27.4%). Conclusion The main findings of our study were that there was no difference between the GM-CSF-enhanced medium and the control group in terms of our major study outcomes. However, blastomere inequality rate and embryo fragmentation rates were lower in the GM-CSF group.


Subject(s)
Humans , Female , Adult , Fertilization in Vitro , Granulocyte-Macrophage Colony-Stimulating Factor , Embryo Culture Techniques , Embryo Transfer
8.
World J Clin Cases ; 10(18): 6338-6340, 2022 Jun 26.
Article in English | MEDLINE | ID: mdl-35949843

ABSTRACT

The application of stem cells is among the many strategies currently available for the treatment of multiple diseases. Stem cells are characterized as undifferentiated cells that have the ability to differentiate towards multiple lineages and self-renewal, among other attributes. Since the first umbilical cord stem cell transplant for the treatment of Fanconi anemia, the use of stem cells for the treatment of multiple diseases, including coronavirus disease 2019, has increased, showing promising results that require evaluation through research studies that include a longer follow-up time. Therefore, the main objective of this Letter is to provide an update on the use of stem cells in the treatment of severe acute respiratory syndrome coronavirus 2, as well as identify the main challenges and limitations presented by this type of therapy.

9.
Rev Med Inst Mex Seguro Soc ; 59(4): 347-351, 2021 Aug 02.
Article in Spanish | MEDLINE | ID: mdl-35019256

ABSTRACT

BACKGROUND: The pulmonary alveolar proteinosis (PAP) is characterized by the accumulation of lipoprotein material in the alveoli. It is classified as primary, secondary and congenital. The primary form, of autoimmune origin, is characterized by antibodies against granulocyte-macrophage colony stimulating factor (GM-CSF). The aim of this article is to present a case of PAP with adequate response to treatment with bronchoalveolar lavage (BAL) and GM-CSF. CLINICAL CASE: A 28-year-old female patient who started with mild to moderate effort dyspnea, distal cyanosis and lower respiratory tract infection. We found restrictive pattern respiratory function tests, chest X-ray with bilateral nodular reticulum pattern and high-resolution tomography with ground glass image and bronchiectasis, besides video bronchoscopy with inflammatory process. The open biopsy revealed data of alveolar proteinaceous material and mononuclear infiltrate. Treatment was given with BAL and GM-CSF which was suspended by dermal reaction. The patient had a satisfactory evolution and is currently asymptomatic. CONCLUSION: The present case had clinical, imaging and histological manifestations for the diagnosis of autoimmune PAP with a satisfactory response to treatment. Although PAP is a low prevalence entity, the diagnosis and therapeutic options must be taken into account, including BAL and GM-CSF, since this factor is required for surfactant factor homeostasis.


INTRODUCCIÓN: la proteinosis alveolar pulmonar (PAP) se caracteriza por la acumulación de material lipoproteináceo en los alveolos, y se clasifica en primaria, secundaria y congénita. La primaria, de origen autoinmune, se caracteriza por anticuerpos contra el factor estimulante de colonia de granulocitos y macrófagos (GM-CSF). El objetivo del presente trabajo es presentar un caso de PAP con buena respuesta al tratamiento con lavado broncoalveolar (LBA) y GM-CSF. CASO CLÍNICO: Caso clínico: distal e infección de vías respiratorias bajas. Se efectuaron pruebas de función respiratoria con patrón restrictivo, radiografía de tórax con patrón retículo nodular bilateral y tomografía de alta resolución con imagen de vidrio despulido y bronquiectasias, así como video broncoscopía con proceso inflamatorio. La biopsia a cielo abierto evidenció datos de material proteináceo alveolar e infiltrado mononuclear. Se dio tratamiento con LBA y GM-CSF, el cual fue suspendido por reacción dérmica. Tuvo evolución satisfactoria y actualmente se encuentra asintomática. CONCLUSIÓN: el presente caso tuvo manifestaciones clínicas, de imagen e histológicas para el diagnóstico de PAP autoinmune con respuesta satisfactoria. Para el tratamiento de la PAP, aunque es una entidad de baja prevalencia, se debe tener en cuenta el diagnóstico y las opciones terapéuticas, entre ellas, el LBA y el GM-CSF, puesto que este factor se requiere para la homeostasis del factor surfactante.


Subject(s)
Pulmonary Alveolar Proteinosis , Adult , Biopsy , Bronchoalveolar Lavage , Bronchoscopy , Female , Humans , Lung , Pulmonary Alveolar Proteinosis/diagnosis , Pulmonary Alveolar Proteinosis/therapy
10.
Neurol Psychiatry Brain Res ; 37: 27-32, 2020 Sep.
Article in English | MEDLINE | ID: mdl-32834527

ABSTRACT

OBJECTIVE: To describe the main neurological manifestations related to coronavirus infection in humans. METHODOLOGY: A systematic review was conducted regarding clinical studies on cases that had neurological manifestations associated with COVID-19 and other coronaviruses. The search was carried out in the electronic databases PubMed, Scopus, Embase, and LILACS with the following keywords: "coronavirus" or "Sars-CoV-2" or "COVID-19" and "neurologic manifestations" or "neurological symptoms" or "meningitis" or "encephalitis" or "encephalopathy," following the Systematic Reviews and Meta-Analyses (PRISMA) guidelines. RESULTS: Seven studies were included. Neurological alterations after CoV infection may vary from 17.3% to 36.4% and, in the pediatric age range, encephalitis may be as frequent as respiratory disorders, affecting 11 % and 12 % of patients, respectively. The Investigation included 409 patients diagnosed with CoV infection who presented neurological symptoms, with median age range varying from 3 to 62 years. The main neurological alterations were headache (69; 16.8 %), dizziness (57, 13.9 %), altered consciousness (46; 11.2 %), vomiting (26; 6.3 %), epileptic crises (7; 1.7 %), neuralgia (5; 1.2 %), and ataxia (3; 0.7 %). The main presumed diagnoses were acute viral meningitis/encephalitis in 25 (6.1 %) patients, hypoxic encephalopathy in 23 (5.6 %) patients, acute cerebrovascular disease in 6 (1.4 %) patients, 1 (0.2 %) patient with possible acute disseminated encephalomyelitis, 1 (0.2 %) patient with acute necrotizing hemorrhagic encephalopathy, and 2 (1.4 %) patients with CoV related to Guillain-Barré syndrome. CONCLUSION: Coronaviruses have important neurotropic potential and they cause neurological alterations that range from mild to severe. The main neurological manifestations found were headache, dizziness and altered consciousness.

11.
Rev. chil. enferm. respir ; Rev. chil. enferm. respir;35(3): 207-218, 2019. graf
Article in Spanish | LILACS | ID: biblio-1058076

ABSTRACT

La Proteinosis Alveolar Pulmonar (PAP) es una enfermedad poco frecuente, caracterizada por la acumulación de material lipoproteico derivado del surfactante pulmonar al interior de los alvéolos por una falla de depuración de este material por los macrófagos alveolares, siendo la causa más frecuente de esta disfunción la acción bloqueadora producida por anticuerpos anti factor estimulante de colonias de granulocitos y macrófagos (GM-CSF) lo que lleva a un deterioro del intercambio gaseoso. La evolución es variable abarcando desde la resolución espontánea hasta la insuficiencia respiratoria grave y la muerte. Se describen tres formas de PAP: Genética, secundaria y autoinmune (antes primaria o idiopática) siendo esta última la más frecuente en adultos. Clínicamente, se manifiesta por disnea, tos seca e hipoxemia que pueden ser progresivas. En la radiografía de tórax se encuentran opacidades bilaterales y la tomografía computarizada de tórax de alta resolución (TACAR) muestra vidrio esmerilado con sobre posición de engrosamiento septal intra e interlobulillar, patrón conocido como "crazy paving". El diagnóstico se basa en la clínica y en el lavado broncoalveolar con material PAS positivo. La biopsia quirúrgica es confirmatoria. El tratamiento clásico es el lavado pulmonar total (LPT) para remover el contenido alveolar. Otras alternativas son la administración de GM-CSF subcutáneo o inhalado, plasmaferesis y rituximab, cuyos resultados son variables. Diferentes autores han modificado la forma del LPT y combinado los diferentes métodos de tratamiento con el fin de obtener resultados más rápidos y efectivos.


Pulmonary Alveolar Proteinosis (PAP) is a rare disease characterized by the accumulation of surfactant derived lipoproteinaceous material filling the alveoli, secondary to failure of its clearance by macrophages. Most of the patients are adults that have auto antibodies directed to Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF). The evolution is towards disturbed gaseous exchange with a wide spectrum of disease from spontaneous recovery to death. There are three forms of PAP: genetic, secondary and autoimmune. Symptoms are scarce and patients may present with dyspnea, dry cough and hypoxemia. Chest X ray shows bilateral opacities and thorax CT depicts ground glass opacities surrounded by septal widening, the so called "crazy paving" pattern. Diagnosis is made on clinical and radiological grounds and confirmed by PAS positive staining of bronchoalveolar lavage material or surgical lung biopsy. Accepted treatment is whole lung lavage (WLL) with saline. Alternatives are subcutaneous or inhaled GM-CSF, Plasmapheresis or Rituximab, and even modification of the method of WLL and combination of different manner of treatment.


Subject(s)
Humans , Pulmonary Alveolar Proteinosis/diagnosis , Pulmonary Alveolar Proteinosis/therapy , Pulmonary Alveolar Proteinosis/etiology , Pulmonary Surfactants/therapeutic use , Granulocyte-Macrophage Colony-Stimulating Factor , Plasmapheresis , Bronchoalveolar Lavage , Rituximab/therapeutic use
12.
Rev. Assoc. Med. Bras. (1992, Impr.) ; Rev. Assoc. Med. Bras. (1992, Impr.);63(12): 1061-1064, Dec. 2017. tab
Article in English | LILACS | ID: biblio-896326

ABSTRACT

Summary Objective: The present study was designed to evaluate safety and efficacy of recombinant human granulocyte colony stimulating factor (G-CSF) injection and whether this regimen could reduce the incidence of adverse events caused by chemotherapy. Method: A total of 100 patients with colon cancer who were treated with chemotherapy in our hospital from January 2011 to December 2014 were randomly divided into two groups, with 50 patients in each group. The patients in the treatment group received G-CSF 24 hours after chemotherapy for consecutive three days; the patients in the control group received the same dose of normal saline. Routine blood tests were performed 7 days and 14 days after chemotherapy. Results: Compared with the control group, the incidences of febrile neutropenia and leukocytopenia in the treatment group were significantly lower (p<0.05). In addition, the incidence of liver dysfunction in the treatment group was lower than that of the control group, without statistical significance. The incidence of myalgia in the treatment was higher than that of the control group without statistical significance. Conclusion: The present study indicated that G-CSF injection after chemotherapy is safe and effective for preventing adverse events in colon cancer patients with chemotherapy.


Subject(s)
Humans , Male , Female , Adult , Aged , Granulocyte Colony-Stimulating Factor/administration & dosage , Granulocyte Colony-Stimulating Factor/adverse effects , Colonic Neoplasms/drug therapy , Chemotherapy-Induced Febrile Neutropenia/prevention & control , Antineoplastic Agents/therapeutic use , Recombinant Proteins/administration & dosage , Recombinant Proteins/adverse effects , Treatment Outcome , Injections , Middle Aged
13.
Braz. j. pharm. sci ; 52(3): 375-382, July-Sept. 2016. tab, graf
Article in English | LILACS | ID: biblio-828262

ABSTRACT

ABSTRACT It is well established that protein malnutrition (PM) impairs immune defenses and increases susceptibility to infection. Macrophages are cells that play a central role in innate immunity, constituting one of the first barriers against infections. Macrophages produce several soluble factors, including cytokines and growth factors, important to the immune response. Among those growth factors, granulocyte-macrophage colony-stimulating factor (GM-CSF) and macrophage colony-stimulating factor (M-CSF). GM-CSF and M-CSF are important to monocyte and macrophage development and stimulation of the immune response process. Knowing the importance of GM-CSF and M-CSF, we sought to investigate the influence of PM on macrophage production of these growth factors. Two-month-old male BALB/c mice were subjected to PM with a low-protein diet (2%) and compared to a control diet (12%) mouse group. Nutritional status, hemogram and the number of peritoneal cells were evaluated. Additionally, peritoneal macrophages were cultured and the production of GM-CSF and M-CSF and mRNA expression were evaluated. To determine if PM altered macrophage production of GM-CSF and M-CSF, they were stimulated with TNF-α. The PM animals had anemia, leukopenia and a reduced number of peritoneal cells. The production of M-CSF was not different between groups; however, cells from PM animals, stimulated with or without TNF-α, presented reduced capability to produce GM-CSF. These data imply that PM interferes with the production of GM-CSF, and consequently would affect the production and maturation of hematopoietic cells and the immune response.


Subject(s)
Rats , Granulocyte-Macrophage Colony-Stimulating Factor/analysis , Macrophage Colony-Stimulating Factor/analysis
14.
Tuberculosis (Edinb) ; 100: 5-14, 2016 09.
Article in English | MEDLINE | ID: mdl-27553405

ABSTRACT

Tuberculosis (TB), although a curable disease, remains a major cause of morbidity and mortality worldwide. It is necessary to develop a short-term therapy with reduced drug toxicity in order to improve adherence rate and control disease burden. Granulocyte-macrophage colony-stimulating factor (GM-CSF) may be a key cytokine in the treatment of pulmonary TB since it primes the activation and differentiation of myeloid and non-myeloid precursor cells, inducing the release of protective Th1 cytokines. In this work, we administrated by intratracheal route recombinant adenoviruses encoding GM-CSF (AdGM-CSF). This treatment produced significant bacterial elimination when administered in a single dose at 60 days of infection with drug sensitive or drug resistant Mtb strains in a murine model of progressive disease. Moreover, AdGM-CSF combined with primary antibiotics produced more rapid elimination of pulmonary bacterial burdens than conventional chemotherapy suggesting that this form of treatment could shorten the conventional treatment.


Subject(s)
Genetic Therapy/methods , Granulocyte-Macrophage Colony-Stimulating Factor/genetics , Tuberculosis, Multidrug-Resistant/therapy , Tuberculosis, Pulmonary/therapy , Adenoviridae/genetics , Animals , Antibiotics, Antitubercular/therapeutic use , Colony Count, Microbial , Combined Modality Therapy , Cytokines/biosynthesis , Cytokines/genetics , Disease Models, Animal , Disease Progression , Gene Expression Regulation , Immunotherapy/methods , Male , Mice, Inbred BALB C , Mycobacterium tuberculosis/growth & development , RNA, Messenger/genetics , Tuberculosis, Multidrug-Resistant/immunology , Tuberculosis, Multidrug-Resistant/microbiology , Tuberculosis, Pulmonary/drug therapy , Tuberculosis, Pulmonary/immunology , Tuberculosis, Pulmonary/microbiology
15.
Mem. Inst. Oswaldo Cruz ; 110(8): 1010-1016, Dec. 2015. graf
Article in English | LILACS | ID: lil-769838

ABSTRACT

T-cell based vaccines against human immunodeficiency virus (HIV) generate specific responses that may limit both transmission and disease progression by controlling viral load. Broad, polyfunctional, and cytotoxic CD4+T-cell responses have been associated with control of simian immunodeficiency virus/HIV-1 replication, supporting the inclusion of CD4+ T-cell epitopes in vaccine formulations. Plasmid-encoded granulocyte-macrophage colony-stimulating factor (pGM-CSF) co-administration has been shown to induce potent CD4+ T-cell responses and to promote accelerated priming and increased migration of antigen-specific CD4+ T-cells. However, no study has shown whether co-immunisation with pGM-CSF enhances the number of vaccine-induced polyfunctional CD4+ T-cells. Our group has previously developed a DNA vaccine encoding conserved, multiple human leukocyte antigen (HLA)-DR binding HIV-1 subtype B peptides, which elicited broad, polyfunctional and long-lived CD4+ T-cell responses. Here, we show that pGM-CSF co-immunisation improved both magnitude and quality of vaccine-induced T-cell responses, particularly by increasing proliferating CD4+ T-cells that produce simultaneously interferon-γ, tumour necrosis factor-α and interleukin-2. Thus, we believe that the use of pGM-CSF may be helpful for vaccine strategies focused on the activation of anti-HIV CD4+ T-cell immunity.


Subject(s)
Animals , Female , Humans , AIDS Vaccines/immunology , Antigens, Viral/immunology , /immunology , Granulocyte-Macrophage Colony-Stimulating Factor/administration & dosage , HIV-1 , Immunity, Cellular/immunology , Vaccines, DNA/immunology , Adjuvants, Immunologic/administration & dosage , /drug effects , Cell Movement/drug effects , Cell Movement/immunology , Conserved Sequence/immunology , Enzyme-Linked Immunospot Assay , Flow Cytometry , Genetic Vectors , Granulocyte-Macrophage Colony-Stimulating Factor/immunology , HIV Infections/prevention & control , HLA-DR Antigens/immunology , Interferon-gamma/drug effects , Interferon-gamma/metabolism , /metabolism , Lymphocyte Activation/drug effects , Lymphocyte Activation/immunology , Mice, Inbred BALB C , Plasmids , Protein Binding/immunology , Tumor Necrosis Factor-alpha/drug effects , Tumor Necrosis Factor-alpha/metabolism
16.
Hum Vaccin Immunother ; 10(11): 3251-60, 2014.
Article in English | MEDLINE | ID: mdl-25483674

ABSTRACT

Adjuvants are a critical but largely overlooked and poorly understood component included in vaccine formulations to stimulate and modulate the desired immune responses to an antigen. However, unlike in the protective infectious disease vaccines, adjuvants for cancer vaccines also need to overcome the effect of tumor-induced suppressive immune populations circulating in tumor-bearing individuals. Myeloid-derived suppressor cells (MDSC) are considered to be one of the key immunosuppressive populations that inhibit tumor-specific T cell responses in cancer patients. This review focuses on the different signals for the activation of the immune system induced by adjuvants, and the close relationship to the mechanisms of recruitment and activation of MDSC. This work explores the possibility that a cancer vaccine adjuvant may either strengthen or weaken the effect of tumor-induced MDSC, and the crucial need to address this in present and future cancer vaccines.


Subject(s)
Adjuvants, Immunologic/therapeutic use , Cancer Vaccines/immunology , Myeloid Cells/immunology , Neoplasms/immunology , Cell Differentiation/immunology , Cytokines/immunology , Dendritic Cells/cytology , Dendritic Cells/immunology , Humans , Intercellular Signaling Peptides and Proteins/immunology , Lymphocyte Activation/immunology , Macrophages/cytology , Macrophages/immunology , Neoplasms/prevention & control , Neoplasms/therapy , T-Lymphocytes/immunology , Vaccination
17.
An. bras. dermatol ; An. bras. dermatol;84(6): 663-666, nov.-dez. 2009. ilus
Article in English, Portuguese | LILACS | ID: lil-538456

ABSTRACT

A síndrome de Sweet pode estar associada a malignidades hematológicas, principalmente, à leucemia mieloide aguda, porém existem poucos relatos demonstrando a associação com a policitemia vera. Relata-se o caso de doente do sexo masculino, de 65 anos, portador de policitemia vera,que evoluiu com aparecimento de síndrome de Sweet na sua forma paraneoplásica.


Sweet’s syndrome may be associated with hematological malignancies, particularly with acute myelogenous leukemia, but there are few reports of its association with polycythemiavera. We describethe case of a 65-year-old male patient, diagnosed with polycythemiavera, which developedinto paraneoplastic Sweet's syndrome.


Subject(s)
Aged , Humans , Male , Polycythemia Vera/complications , Sweet Syndrome/etiology
18.
Iatreia ; Iatreia;7(4): 173-180, dic. 1994. graf
Article in English, Spanish | LILACS | ID: lil-434346

ABSTRACT

Los factores de crecimiento hematopoyético {FCH) son producto de la excitante y prometedora industria de la biología molecular y la Ingeniería genética. Se hace una revisión de la farmacología del Factor Estimulador de Colonias de Granulocitos y del Factor Estimulador de Colonias de Granulocitos-Macrófagos, como también de su uso clínico en neutropenia aguda post-quimioterapia mielotóxica anticancerosa, trasplante de médula ósea, leucemia aguda, síndromes mielodisplásicos, anemia aplástica, síndrome de inmunodeficiencia adquirida y neutropenia crónica.


Hematopoietic growth factors are one of the products of the exciting and promising molecular biology and genetic engineering industries. Two of these factors are the recombinant human - granulocyte colony-stimulating factor and the recombinant human-granulocyte-macrophage colony-stimulating factor; a review Is presented on their pharmacology and clinical uses in acute neutropenia after myelotoxic anticancer therapy, bone marrow transplantion, acute leukemia, myelodyplastic syndromes, aplastic anemia, AIDS and chronic neutropenia


Subject(s)
Thrombocytopenia , Granulocyte Colony-Stimulating Factor , Granulocyte-Macrophage Colony-Stimulating Factor , Neutropenia , Hematopoietic Cell Growth Factors
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