RESUMO
Diabetes is a risk factor for the development of pulmonary tuberculosis (TB) and both diseases present endocrine alterations likely to play a role in certain immuno-endocrine-metabolic associated disorders. Patients with TB, or with TB and type 2 diabetes (TB + T2DM) and healthy controls (HCo) were assessed for plasma levels of cortisol, dehydroepiandrosterone (DHEA), estradiol, testosterone, growth hormone (GH), prolactin, insulin-like growth factor-1 (IGF-1), cytokines (IL-6, IL-10, IFN-γ) and the specific lymphoproliferative capacity of peripheral blood mononuclear cells. All patients had higher levels of cortisol with a reduction in DHEA, thus resulting in an increased cortisol/DHEA ratio (Cort/DHEA). Increased prolactin and particularly GH levels were found in both groups of TB patients. This was not paralleled by increased concentrations of IGF, which remained within the levels of HCo. Estradiol levels were significantly augmented in patients TB, and significantly more in TB + T2DM, whereas testosterone levels were decreased in both groups of patients. IFN- γ and IL-6 concentrations were significantly increased in all TB, even further in TB + T2DM; while IL-10 was equally increased in both groups of TB patients. The in vitro specific proliferative capacity was decreased in both groups of patients as compared to that of HCo. The adverse immune-endocrine profile of TB seems to be slightly more pronounced in patients who also have T2DM.
Assuntos
Citocinas/sangue , Diabetes Mellitus Tipo 2/sangue , Hormônios/sangue , Infecções Oportunistas/sangue , Tuberculose Pulmonar/sangue , Adulto , Estudos de Casos e Controles , Células Cultivadas , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/imunologia , Feminino , Humanos , Ativação Linfocitária , Masculino , Pessoa de Meia-Idade , Infecções Oportunistas/complicações , Infecções Oportunistas/imunologia , Tuberculose Pulmonar/complicações , Tuberculose Pulmonar/imunologiaRESUMO
BACKGROUND: Tuberculosis (TB) is a infectious disease characterised by a profound immune-endocrine metabolic imbalance, including a diminution in leptin plasma levels. Leptin appears to be the link between nutritional status and the development of a protective immune response. OBJECTIVE: To examine the effects of leptin on the proliferation and production of interferon-gamma (IFN-γ) by peripheral blood mononuclear cells (PBMC) in TB patients and healthy controls stimulated with mycobacterial antigens with or without leptin. As macrophages are key cells in mycobacterial containment, the effect of leptin on the production of interleukin (IL) 1ß and IL-1Ra by the monocytic cell line THP-1 was also studied. RESULTS: Leptin diminished the proliferative capacity of PBMC on mycobacterial stimulation, and had no effect on IFN-γ production in terms of measurements in culture supernatants or intracytoplasmic analysis using flow cytometry. Real-time polymerase chain reaction studies of PBMC from TB patients revealed a preserved expression of leptin receptor. Furthermore, IL-1ß and IL-1Ra secretion by THP-1 cells was not modified by leptin treatment. CONCLUSION: The study results do not support the utility of treatment with leptin to correct immune imbalances due to TB.
Assuntos
Antígenos de Bactérias/imunologia , Interferon gama/imunologia , Leptina/farmacologia , Tuberculose/imunologia , Adulto , Estudos de Casos e Controles , Linhagem Celular , Feminino , Humanos , Imunidade Celular , Proteína Antagonista do Receptor de Interleucina 1/metabolismo , Interleucina-1beta/metabolismo , Leucócitos Mononucleares/imunologia , Masculino , Monócitos/efeitos dos fármacos , Monócitos/imunologia , Mycobacterium tuberculosis/imunologia , Reação em Cadeia da Polimerase em Tempo Real , Adulto JovemRESUMO
Tuberculosis (TB) may be regarded as a disease in which the immune response to Mycobacterium tuberculosis, its etiologic agent, is engaged both in protection and pathology. Different T-lymphocyte subsets are involved in the immune response against M. tuberculosis, but production of interferon-gamma (IFN-gamma) by T cells seems to be fundamental for disease control. Th1-type cytokine responses predominate in patients with mild or moderate forms of pulmonary TB, whereas the production of Th2-type cytokines prevails in the severe disease. Since the immune response fails to definitely eradicate the pathogen, a chronic infection is established, and it is likely that a broad range of regulatory mechanisms operate in this situation. Cytokines released during the course of an immune response activate the hypothalamus-pituitary-adrenal axis leading to the production of glucocorticoids and dehydroepiandrosterone (DHEA), with known immunomodulatory effects. TB patients exhibit increased concentrations of interleukin-6 and cortisol in plasma, reduced DHEA and testosterone levels, together with remarkably increased growth hormone concentrations that were not accompanied by an expected raise in insulin-like growth factor-1. Significant increases in estradiol, prolactin, and thyroid hormone concentrations were also detected in patients. Cortisol inhibits the mycobacterial antigen-driven proliferation and IFN-gamma production, whereas DHEA suppresses transforming growth factor beta production by lymphoid cells from TB patients with advanced disease. Furthermore, supernatants from cultures of M. tuberculosis-stimulated mononuclear cells of TB patients inhibit DHEA secretion by a human adrenal cell line. This type of immuno-endocrine interactions may affect the control of tissue damage and the development of protective immune responses, partly accounting for disease aggravation.
Assuntos
Sistemas Neurossecretores/imunologia , Sistemas Neurossecretores/metabolismo , Tuberculose Pulmonar/imunologia , Tuberculose Pulmonar/metabolismo , Animais , Citocinas/metabolismo , Citocinas/fisiologia , Humanos , Tuberculose Pulmonar/microbiologia , Tuberculose Pulmonar/patologiaRESUMO
Peripheral blood mononuclear cells taken from 32 patients with Rheumatoid Arthritis (RA) receiving neither steroids nor methotrexate and 34 healthy controls were examined for lymphoproliferation in the presence of ultrasonic extracts of 14 different mycobacterial species or serotypes, of an extract of Candida albicans and of 2 mitogens. Additionally, cells were incubated for 96 hours alone, or with Mycobacterium tuberculosis (M.tb) sonicate or Concanavalin-A (Con-A), and supernatants were tested for a range of cytokines. Lymphocytes of rheumatoid patients were less reactive than controls to all the mycobacterial preparations, but no different in their responses to mitogens. Stimulation of patients' cells with M.tb sonicate induced significantly less interferon-gamma (IFN-gamma), tumour necrosis factor-alpha (TNF-alpha) and interleukin-10 (IL-10) but more transforming growth factor- beta (TGF-beta) than controls. Even stimulation with Con-A induced much less IFN-gamma in patient's cells than in those of controls. The combination of reduced responses to the mycobacterial reagents and reduced stimulation of type 1 cytokines by the sonicate of M.tb, suggests reduced responsiveness to group i, common mycobacterial antigens. Such findings need not indicate involvement of mycobacteria specifically in the disease aetiology, but provide novel information on the immunopathological abnormalities, which may explain the reported increased susceptibility to mycobacteria of RA patients.
Assuntos
Artrite Reumatoide/imunologia , Citocinas/biossíntese , Inflamação/sangue , Interferon gama/biossíntese , Leucócitos/microbiologia , Mycobacteriaceae/imunologia , Adulto , Candida albicans/imunologia , Epitopos , Feminino , Humanos , Técnicas In Vitro , Mononucleose Infecciosa/imunologia , Ativação Linfocitária/efeitos dos fármacos , Masculino , Pessoa de Meia-Idade , Mitógenos/imunologia , Linfócitos T/imunologiaRESUMO
The effect of cortisol and/or dehydroepiandrosterone (DHEA) on the immune response to antigens obtained from Mycobacterium tuberculosis was studied in vitro by using peripheral blood mononuclear cells obtained from patients at various stages of lung tuberculosis (TB) and from healthy control people (HCo). The results obtained show for the first time that addition of cortisol within concentrations of physiological range can inhibit the mycobacterial antigen-driven proliferation of cells from HCo and TB patients and the production of interferon-gamma (IFN-gamma), indicating that endogenous levels of cortisol may contribute to the decreased lymphoid cell response to mycobacterium antigens observed in TB patients. DHEA did not affect lymphoid cell proliferation, IFN-gamma production and the cortisol-mediated inhibitory effects. Interestingly, we found that DHEA, but not cortisol, suppressed the in vitro transforming growth factor-beta production by lymphoid cells from TB patients with an advanced disease, which is indicative of a selective direct effect of this hormone.
Assuntos
Adjuvantes Imunológicos/farmacologia , Anti-Inflamatórios/farmacologia , Antígenos de Bactérias/imunologia , Desidroepiandrosterona/farmacologia , Hidrocortisona/farmacologia , Leucócitos Mononucleares/efeitos dos fármacos , Tuberculose/tratamento farmacológico , Adulto , Idoso , Divisão Celular/imunologia , Citocinas/metabolismo , Feminino , Humanos , Leucócitos Mononucleares/imunologia , Leucócitos Mononucleares/metabolismo , Masculino , Pessoa de Meia-Idade , Mycobacterium tuberculosis/imunologia , Tuberculose/imunologiaRESUMO
Animal and technical models often require repeated anaesthetic administrations for surgical procedures. As there is evidence for immunomodulatory effects of anaesthesia, the effects of repeated exposure to sevoflurane anaesthesia on the immune response in mice were studied. Sevoflurane was administered in vivo under conditions that simulate those in clinical procedures. Adult male mice were anaesthetized with 3% sevoflurane in oxygen for 40 min weekly for 3 weeks. Untreated animals served as controls. After sevoflurane anaesthesia, peripheral blood leukocyte counts, the composition and in vitro function of spleen cells (lymphocytes and macrophages) and the in vivo immune response to a conventional T-dependent antigen were assessed. In addition, liver, spleen and kidney histopathology and also hepatic and renal function were studied. Three days after the latest anaesthetic procedure, the absolute number of both leukocyte and lymphocyte counts were reduced in peripheral blood. Splenic cell composition (LB, LTCD3(+), LTCD4(+) and LTCD8(+)), macrophage function and the mitogen-induced lymphoprolipherative response were preserved. Yet, the in vivo humoral response to a conventional antigen was augmented following the antigenic challenge. Assessment at day 9 after the last anaesthetic procedure revealed the persistence of the humoral response alteration. Nevertheless, sevoflurane-treated animals showed no evidence of histological changes or alteration in hepatic or renal function.
Assuntos
Anestesia , Anestésicos Inalatórios/efeitos adversos , Imunidade/efeitos dos fármacos , Éteres Metílicos/efeitos adversos , Animais , Linfócitos B , Rim/anatomia & histologia , Rim/efeitos dos fármacos , Rim/fisiologia , Contagem de Leucócitos , Fígado/anatomia & histologia , Fígado/efeitos dos fármacos , Fígado/fisiologia , Contagem de Linfócitos , Macrófagos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Sevoflurano , Baço/citologia , Linfócitos T , Timo/anatomia & histologia , Timo/efeitos dos fármacosRESUMO
Based on the immunomodulatory effects of anesthesia and surgery, a study was undertaken to assess the effect of sevoflurane anesthesia on the immune system in a murine model without surgery. Adult male mice were anesthetized with 3% sevoflurane (1.2 minimal alveolar concentration, MAC) in oxygen for 40 min, whereas nontreated animals served as controls. After sevoflurane anesthesia, peripheral blood leukocyte counts, the splenic composition and in vitro macrophage phagocytic activity and lymphoproliferative response were assessed. The in vivo specific immune response to sheep red blood cells (SRBC), a conventional T-dependent antigen was determined. In addition, liver, spleen, thymus and kidney histopathology and also hepatic and renal functions after anesthesia were studied. Sevoflurane diminished the number of peripheral blood lymphocytes and splenic B-cell counts, enhancing CD4+ lymphocytes in spleen. The in vitro functionality of macrophages and the mitogen-induced lymphoproliferative response were preserved, while the in vivo immune response to SRBC was enhanced in treated animals. Microscopic studies revealed conserved architecture of the spleen, thymus, lymph node, liver and kidney, and there were no differences in serum parameters of hepatic and renal functions between treated and control groups. Our results suggest that 3 days after the anesthetic exposure, animals treated with sevoflurane modulated their peripheral blood leukocyte counts, splenic lymphoid composition and the characteristics of the specific response to SRBC, while there was no evidence of hepatic or renal toxicity.
Assuntos
Adjuvantes Imunológicos , Anestesia Geral , Anestésicos Inalatórios/farmacologia , Éteres Metílicos/farmacologia , Anestésicos Inalatórios/toxicidade , Animais , Linfócitos B/efeitos dos fármacos , Contagem de Células Sanguíneas , Candida/imunologia , Divisão Celular/efeitos dos fármacos , Feminino , Imunidade Celular/efeitos dos fármacos , Testes de Função Renal , Contagem de Leucócitos , Testes de Função Hepática , Contagem de Linfócitos , Masculino , Éteres Metílicos/toxicidade , Camundongos , Tamanho do Órgão/efeitos dos fármacos , Gravidez , Sevoflurano , Baço/citologia , Baço/efeitos dos fármacos , Baço/imunologia , Linfócitos T/efeitos dos fármacos , Linfócitos T/imunologia , Teratogênicos/toxicidadeRESUMO
Earlier studies in patients with pulmonary TB have revealed a higher production of Th1 cell type cytokines in moderate TB, with predominant Th2-like responses in advanced disease. Given the influence of IL-12 in T cell differentiation, as well as the roles of transforming growth factor-beta (TGF-beta), nitric oxide and tumour necrosis factor-alpha (TNF-alpha) in the immune response against intracellular pathogens, we decided to analyse the interferon-gamma (IFN-gamma), IL-4, IL-12, TGF-beta, TNF-alpha and nitrite concentrations in culture supernatants of PBMC from TB patients showing different degrees of lung involvement. The sample population comprised 18 untreated TB patients with either moderate (n = 9) or advanced (n = 9) disease and 12 age- and sex-matched healthy controls (total population (patients and controls) 12 women, 18 men, aged 37 +/- 13 years (mean +/- s.d.)). PBMC were stimulated with whole sonicate from Mycobacterium tuberculosis and the supernatants were collected on day 4 for measurement of cytokine and nitrite levels. Antigen-stimulated IFN-gamma, TGF-beta and TNF-alpha production was found to be significantly increased in TB patients, both moderate and advanced, compared with the controls. Levels of IFN-gamma were significantly higher in moderate disease than advanced cases, whereas advanced cases showed significantly higher IL-12, TGF-beta and TNF-alpha concentrations when compared with cases of moderate TB. Nitrite levels were also increased in TB patients and the increase was statistically significant when advanced cases were compared with controls. These findings may contribute to a clearer picture of the net effect of cytokine interactions in TB, essential for a better understanding of the immunopathological mechanisms underlying the distinct clinical forms of the disease.
Assuntos
Citocinas/biossíntese , Nitritos/metabolismo , Tuberculose Pulmonar/imunologia , Adolescente , Adulto , Idoso , Células Cultivadas , Feminino , Humanos , Interferon gama/biossíntese , Interleucina-12/biossíntese , Interleucina-4/biossíntese , Leucócitos Mononucleares/citologia , Leucócitos Mononucleares/imunologia , Leucócitos Mononucleares/microbiologia , Masculino , Pessoa de Meia-Idade , Mycobacterium tuberculosis/imunologia , Fator de Crescimento Transformador beta/biossíntese , Tuberculose Pulmonar/sangue , Tuberculose Pulmonar/fisiopatologia , Fator de Necrose Tumoral alfa/biossínteseRESUMO
Given the role of cell-mediated immune responses in resistance to mycobacteria, we sought to analyse whether there was a relationship between the severity of pulmonary tuberculosis (TB) and lymphocyte proliferation as well as in vitro cytokine production. To achieve this, 25 untreated TB patients showing mild (n = 5), moderate (n = 9) or advanced (n = 11) pulmonary disease, and 12 age-matched healthy controls (mean+/-SD, 37+/-14.5 years) were studied. Peripheral blood mononuclear cells were cultured for 5 days with 10 microg/ml whole, sonicated Mycobacterium tuberculosis (WSA) or 2.5 microg/ml Concanavalin A (Con A). Supernatants were collected on day 4, from cultures grown with or without WSA, for measurement of interferon-gamma (IFN-gamma), interleukin (IL)-4, IL-1beta and transforming growth factor-beta (TGF-beta). Antigen-specific proliferation was found to be reduced among patients and more profound in those with advanced disease who also displayed a depressed response to Con A. Patients with mild TB showed a preferential production of IFN-gamma over IL-4, gave the highest level of IFN-gamma synthesis upon specific antigen stimulation and showed increased levels of IL-1beta production. Findings in patients with moderate TB appeared compatible with a mixed production of IFN-gamma and IL-4 coexisting with a higher synthesis of TGF-beta, by comparison to patients with mild TB. Advanced disease showed the highest IL-4 and TGF-beta production, with IFN-gamma synthesis readily noticeable, yet decreased in comparison with the other patient groups. Differences in cytokine response according to the amount of lung involvement suggest a role for such mediators in the immunopathogenesis underlying the distinct clinical forms of pulmonary TB, that is a predominant T helper Th)1-like or Th2-like activity in mild or in progressive TB, respectively.
Assuntos
Interferon gama/biossíntese , Interleucina-1/biossíntese , Interleucina-4/biossíntese , Leucócitos Mononucleares/metabolismo , Fator de Crescimento Transformador beta/biossíntese , Tuberculose/imunologia , Adolescente , Adulto , Idoso , Antígenos de Bactérias/farmacologia , Células Cultivadas , Concanavalina A/farmacologia , Feminino , Humanos , Interferon gama/sangue , Interleucina-1/sangue , Interleucina-4/sangue , Pneumopatias/sangue , Ativação Linfocitária , Masculino , Pessoa de Meia-Idade , Mycobacterium tuberculosis/imunologia , Índice de Gravidade de Doença , Estatísticas não Paramétricas , Linfócitos T/citologia , Linfócitos T/imunologia , Fator de Crescimento Transformador beta/sangue , Tuberculose/sangueRESUMO
Heparinised blood samples were obtained from 20 patients with chronic plaque psoriasis and from 13 age-matched healthy controls. After preliminary titration, mononuclear cells separated over Ficoll-Tryoson were cultured for 5 days with 10 microg ml(-1) of 15 mycobacterial preparations, or with pokeweed mitogen and concanavalin A. Stimulation indices were determined for each reagent and means were determined for patients and controls. Results for patients showed a striking reduction of responsiveness to mycobacteria, apparently due to loss of responses to group i, common mycobacterial antigens, and no differences in responses to mitogens. These observations relate psoriasis to certain other diseases, notably mycobacterial infections, rheumatoid arthritis, Chagas' disease and human immunodeficiency virus infection. The observations may be relevant to the aetiology of psoriasis, and to potential immunotherapy for the disease.
Assuntos
Antígenos de Bactérias/imunologia , Ativação Linfocitária , Mycobacterium/imunologia , Psoríase/imunologia , Linfócitos T/imunologia , Adulto , Células Cultivadas , Concanavalina A/imunologia , Feminino , Humanos , Masculino , Análise por Pareamento , Mitógenos de Phytolacca americana/imunologia , Psoríase/sangueRESUMO
A placebo-controlled study of immunotherapy with Mycobacterium vaccae for chronic plaque psoriasis showed improvement in the psoriasis area severity index in 19 of 21 immunotherapy recipients (P<0.005). Minor improvement, not reaching statistical significance for the group, occurred in nine of 14 placebo recipients. There were losses to follow-up and the placebo used, tetanus toxoid, was not ideal. Clinical improvement after immunotherapy persisted for 6 months and another injection of the immunotherapeutic given to a few volunteers from either group resulted in benefits lasting a year. Lymphoproliferative tests were carried out at each clinic visit, and on 50 matched controls. Starting with reduced responses to mycobacterial antigens and concanavalin A, both treatment groups showed a fall after 3 months, and diverged at 6 months with M. vaccae recipients rising to values similar to those of healthy controls, whereas placebo recipients continued to fall. Conclusions reached were that immunotherapy with M. vaccae gave long-lasting clinical benefit to most patients, with minimal side effects. This accompanied a return towards normal cellular immune responsiveness to mycobacterial antigens, which did not follow the use of the placebo.
Assuntos
Antígenos de Bactérias/imunologia , Proteínas de Bactérias , Imunoterapia Ativa , Mycobacterium/imunologia , Psoríase/terapia , Adulto , Anticorpos Antibacterianos/sangue , Células Cultivadas , Chaperonina 60 , Chaperoninas/imunologia , Concanavalina A/imunologia , Ensaio de Imunoadsorção Enzimática , Humanos , Ativação Linfocitária/imunologia , Mycobacterium avium/imunologia , Mycobacterium tuberculosis/imunologia , Psoríase/imunologia , Índice de Gravidade de DoençaRESUMO
To evaluate the status of the cellular immune response of patients with community acquired pneumonia (CAP), 8 CAP cases were studied for their in vitro T-cell responses to concanavalin A (Con A), tuberculin, and candidin, as well as levels of major T-cell populations in peripheral blood. Assessment on admission revealed that CAP patients had significantly decreased responses to both antigen and mitogen driven lymphocyte proliferation when compared to age and sex matched controls. Studies performed upon 1 week of antibiotic treatment made evident, in turn, that clinical improvement was accompanied by a reestablishment of the in vitro responses to tuberculin and candidin, whereas the lymphoproliferation induced by Con A remained decreased as in its first evaluation. Data from admission and day 7 of treatment showed no significant differences as to the levels of peripheral T-cell subsets when compared to those of healthy controls. Our results indicate that CAP coincides with reduced in vitro T-cell responses to antigen and mitogen stimulation.
Assuntos
Infecções Comunitárias Adquiridas/imunologia , Macrolídeos , Pneumonia Bacteriana/imunologia , Linfócitos T/imunologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Amoxicilina/uso terapêutico , Animais , Antibacterianos/farmacologia , Infecções Comunitárias Adquiridas/tratamento farmacológico , Concanavalina A/farmacologia , Feminino , Humanos , Ativação Linfocitária , Masculino , Pessoa de Meia-Idade , Penicilinas/uso terapêutico , Pneumonia Bacteriana/tratamento farmacológico , Ratos , Subpopulações de Linfócitos T/imunologia , Tuberculina/farmacologiaRESUMO
The extent of surgery, the patient's age, health status and other factors may contribute to alteration of the immune system during anesthesia and surgery. In addition, inhalatory anesthetics may cause acute and chronic toxicity because of the production of intermediate and end metabolic compounds. The present work was undertaken to evaluate, both in vivo and in vitro, if repeated doses of halothane were able to affect the immune response in a murine model developed at our laboratory. Weekly doses of halothane were administered to mice subjected to no surgery and three days after the last anesthetic-exposure, several immunologic parameters were assessed. Results on the in vivo response to sheep red blood cells showed that halothane treatment increased the amount of specific antibody secreting B-cells, without affecting the delayed type hypersensitivity reaction to the same antigen. In vitro studies on spleen cell composition showed that halothane re-exposure diminished the number of CD4+, CD8+ and B-cells. Such changes were not translated into alterations on the mitogen-driven lymphoproliferation, as well as macrophage phagocytic and lytic functions. Our results indicate that halothane re-exposure is able to modulate the immune response affecting both the number of antibody secreting cells involved in a specific in vivo response, and the splenic lymphoid cell composition. Since such halothane-induced immune alterations might bias the results of a wide range of physiological research, even those involving other systems, a careful selection of the anesthetic agent and methods by which the compound is administered is advisable.
Assuntos
Anestésicos Inalatórios/farmacologia , Halotano/farmacologia , Baço/efeitos dos fármacos , Animais , Subpopulações de Linfócitos/efeitos dos fármacos , Linfócitos/efeitos dos fármacos , Linfócitos/imunologia , Masculino , Camundongos , Camundongos Endogâmicos , Fagocitose/efeitos dos fármacos , Baço/imunologiaRESUMO
Concomitant immunity (IC) is usually defined as the capacity of any animal bearing a progressor tumor to inhibit a second challenge with the same tumor. In order to establish the contribution of the host to the origin of this phenomenon, IC was induced in two lines of rats with a different behavior when challenged with Sarcoma E 100 (SE 100), i.e., line IIMc: 90% take and 100% regression; line "m": 100% take and death. The rats received a second challenge on day 3 (Group II), 7 (III), and 14 (IV), as well as the control groups: II', III' and IV', respectively. The animals reinoculated on day 7 showed a decrease, both in percentage of takes (Fig. 1, III vs III') and tumor surface (Table 1, 2). Likewise, in rats IIMc, a lesser development of the first inoculum (Table 1, Ia vs I') was observed. The Winn assay (Table 3) confirmed the presence of immunocompetent spleen cells (CE) against SE 100 in IIMc rat spleens: namely, 1) immune rats (II), 2) unique tumor bearing rats (IV), 3) first progressor and second negative inoculum (V). In line "m" the percentage of takes was only smaller in the group inoculated conjointly with CE from immune rats (Table 3, VI vs VII). A mere 10% (3/30) of "m" rats were immunized against SE 100. Consequently, these results could attribute the IC, in IIMc rats, to immunological mechanisms, while in "m" it could be due to factor(s) released and/or induced by the first tumor, as proposed by Gorelik.
Assuntos
Rejeição de Enxerto/imunologia , Sarcoma Experimental/imunologia , Neoplasias Esplênicas/imunologia , Animais , Imunidade Celular , Masculino , Transplante de Neoplasias/imunologia , RatosRESUMO
Concomitant immunity (IC) is usually defined as the capacity of any animal bearing a progressor tumor to inhibit a second challenge with the same tumor. In order to establish the contribution of the host to the origin of this phenomenon, IC was induced in two lines of rats with a different behavior when challenged with Sarcoma E 100 (SE 100), i.e., line IIMc: 90
take and 100
regression; line [quot ]m[quot ]: 100
take and death. The rats received a second challenge on day 3 (Group II), 7 (III), and 14 (IV), as well as the control groups: II, III and IV, respectively. The animals reinoculated on day 7 showed a decrease, both in percentage of takes (Fig. 1, III vs III) and tumor surface (Table 1, 2). Likewise, in rats IIMc, a lesser development of the first inoculum (Table 1, Ia vs I) was observed. The Winn assay (Table 3) confirmed the presence of immunocompetent spleen cells (CE) against SE 100 in IIMc rat spleens: namely, 1) immune rats (II), 2) unique tumor bearing rats (IV), 3) first progressor and second negative inoculum (V). In line [quot ]m[quot ] the percentage of takes was only smaller in the group inoculated conjointly with CE from immune rats (Table 3, VI vs VII). A mere 10
(3/30) of [quot ]m[quot ] rats were immunized against SE 100. Consequently, these results could attribute the IC, in IIMc rats, to immunological mechanisms, while in [quot ]m[quot ] it could be due to factor(s) released and/or induced by the first tumor, as proposed by Gorelik.
RESUMO
A high mortality rate for lung cancer (62.7 per 100,000) is found in Rosario, Argentina. To investigate the reasons for this high rate, a case-control study was carried out among 215 male cases with histologically confirmed lung cancer and 433 hospitalized controls for conditions unrelated to tobacco consumption. Odds ratios (OR) of squamous cell (SQ), adenocarcinoma (AD), and small cell (SM) carcinoma of the lung associated with different characteristics of the smoking habit were quantified. Ninety-eight percent of the cases had smoked regularly. Smokers were significantly younger at diagnosis than ex-smokers (P < 0.0001), a pattern consistent for all cell types. The ORs for the heaviest cf the lowest consumption categories were 15.3 for SQ, 11.6 for AD, and 11.6 for all lung cancer (P < 0.0001). Risks associated with the use of unfiltered cigarettes were three to five times higher than those for filtered cigarettes, depending on cell types. For ex-smokers, risks after 10 years of nonsmoking were about 12 times lower than those of current smokers (P < 0.001). To halt further increases in lung cancer, preventive measures in Argentina should be directed primarily towards smoking control.
Assuntos
Adenocarcinoma/epidemiologia , Carcinoma de Células Pequenas/epidemiologia , Carcinoma de Células Escamosas/epidemiologia , Neoplasias Pulmonares/epidemiologia , Fumar/efeitos adversos , Adenocarcinoma/etiologia , Adenocarcinoma/patologia , Adulto , Fatores Etários , Argentina/epidemiologia , Carcinoma de Células Pequenas/etiologia , Carcinoma de Células Pequenas/patologia , Carcinoma de Células Escamosas/etiologia , Carcinoma de Células Escamosas/patologia , Estudos de Casos e Controles , Humanos , Modelos Logísticos , Neoplasias Pulmonares/etiologia , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Fumar/epidemiologia , Prevenção do Hábito de FumarRESUMO
The removal of active phagocytic cells (CFA) from suspensions of a rat sarcoma (S-E 100) caused a decrease in tumor development in "m" line rats; consequently, we postulated that the macrophage (M phi) population infiltrating the tumor might possess inhibitory functions. In the present paper we investigate whether the effect of CFA is a general one or whether it is dependent on the interaction between M phi infiltrating the tumor and the recipient. S-E 100 was inoculated in "m" line rats (S-E 100,m) and in "c" (S-E 100,c); CFA were depleted from both tumoral suspensions with carbonyl iron powder (FeC), inoculating the supernatant tumor sells denominated S.FeC-m and S.FeC-c, and the corresponding control suspensions, S Te-m and S Te-c. Inocula for both recipients were subcutaneous and contained 1 x 10(6) cells. The elimination of CFA induced a decrease in the development of the tumor in "m" recipients only when the inoculum was provided by S-E 100, m (Table 1). On the contrary no change in tumor growth was detected in the "C" recipients, whether the inoculum was provided by SE-100, m or by S-E 100, c (Table 1). An inhibitory effect on the immune response exerted by M phi infiltrating S-E 100, as a non general effect, is postulated. This effect was obtained only when intratumoral M phi were syngeneic with the recipient and specifically for "m" line.
Assuntos
Macrófagos/fisiologia , Sarcoma Experimental/patologia , Animais , Feminino , Imunidade Celular , Macrófagos/transplante , Masculino , Transplante de Neoplasias , Ratos , Ratos Endogâmicos/imunologia , Sarcoma Experimental/imunologiaRESUMO
The removal of active phagocytic cells (CFA) from suspensions of a rat sarcoma (S-E 100) caused a decrease in tumor development in [quot ]m[quot ] line rats; consequently, we postulated that the macrophage (M phi) population infiltrating the tumor might possess inhibitory functions. In the present paper we investigate whether the effect of CFA is a general one or whether it is dependent on the interaction between M phi infiltrating the tumor and the recipient. S-E 100 was inoculated in [quot ]m[quot ] line rats (S-E 100,m) and in [quot ]c[quot ] (S-E 100,c); CFA were depleted from both tumoral suspensions with carbonyl iron powder (FeC), inoculating the supernatant tumor sells denominated S.FeC-m and S.FeC-c, and the corresponding control suspensions, S Te-m and S Te-c. Inocula for both recipients were subcutaneous and contained 1 x 10(6) cells. The elimination of CFA induced a decrease in the development of the tumor in [quot ]m[quot ] recipients only when the inoculum was provided by S-E 100, m (Table 1). On the contrary no change in tumor growth was detected in the [quot ]C[quot ] recipients, whether the inoculum was provided by SE-100, m or by S-E 100, c (Table 1). An inhibitory effect on the immune response exerted by M phi infiltrating S-E 100, as a non general effect, is postulated. This effect was obtained only when intratumoral M phi were syngeneic with the recipient and specifically for [quot ]m[quot ] line.