RESUMO
Arachidonic acid can be transformed into a series of HPETEs by the lipoxygenase enzyme activity of mouse peritoneal macrophages. These resulting HPETEs inhibit some mouse lymphocyte responses. When mice are injected with 15-L-HPETE, their splenocytes show a decreased [3H]thymidine uptake after lectin stimulation.
Assuntos
Ácidos Araquidônicos/farmacologia , Leucotrienos , Peróxidos Lipídicos , Linfócitos/efeitos dos fármacos , Animais , Ácidos Araquidônicos/metabolismo , Feminino , Lectinas/farmacologia , Lipoxigenase/metabolismo , Linfócitos/imunologia , Linfócitos/fisiologia , Camundongos , Camundongos Endogâmicos C57BL , Baço/efeitos dos fármacos , Timidina/metabolismoRESUMO
There is some evidence that treatment with interleukin-2 (IL-2) and interferon-alpha (IFNalpha) frequently induces depressive symptoms and activation of the inflammatory response system (IRS). There is evidence that major depression is accompanied by lowered serum activity of dipeptidyl peptidase IV (DPP IV; EC 3.4.14.5), a membrane-bound serine protease which catalyses the cleavage of some cytokines and neuro-active peptides and which modulates T cell activation and the production of cytokines, such as IL-2. This study was carried out to examine the effects of immunochemotherapy with IL-2 and IFNalpha, alone and together, in cancer patients on serum DPP IV activity in relation to changes in depressive symptoms and the IRS. The Montgomery and Asberg Rating Scale (MADRS), serum DPP IV activity, and the serum IL-6, and IL-2 receptor (IL-2R) concentrations were measured in 26 patients with metastatic cancers before and three and five days after treatment with IL-2 and IFNalpha, alone or together. Treatment with IL-2 with or without IFNalpha significantly suppressed serum DPP IV activity. The MADRS scores were significantly elevated by treatment with IL-2 with or without IFNalpha, but not IFNalpha alone. The immunochemotherapy-induced decreases in serum DPP IV were significantly and inversely correlated with the increases in the MADRS. Treatment with IL-2 alone or combined with IFNalpha also elevated serum IL-6 and IL-2R. There were significant and inverse correlations between the immuchemotherapy-induced decreases in serum DPP IV and the elevations in serum IL-6 or IL-2R. In conclusion, treatment with IL-2/IFNalpha decreases serum DPP IV activity within 3-5 days and the immunochemotherapy-induced decreases in serum DPP IV activity are significantly and inversely related to treatment-induced increases in severity of depression and signs of activation of the IRS.
Assuntos
Carcinoma/sangue , Depressão/sangue , Dipeptidil Peptidase 4/efeitos dos fármacos , Interleucina-2/farmacologia , Melanoma/sangue , Receptores de Interleucina-2/efeitos dos fármacos , Adulto , Idoso , Análise de Variância , Antineoplásicos/uso terapêutico , Carcinoma/tratamento farmacológico , Citocinas/sangue , Citocinas/efeitos dos fármacos , Dipeptidil Peptidase 4/sangue , Feminino , Humanos , Imunoterapia , Interferon-alfa/uso terapêutico , Interleucina-2/uso terapêutico , Masculino , Melanoma/tratamento farmacológico , Pessoa de Meia-Idade , Receptores de Interleucina-2/sangueRESUMO
PURPOSE: To evaluate the radiosensitivity of self-renewing progenitor cells in acute myeloblastic leukemia (AML), we have compared the radiosensitivity of the cells grown either in methylcellulose alone for 7 days, or first in suspension culture for 7 days before being plated in methylcellulose. Methylcellulose selects for terminal-dividing cells and suspension cultures have been developed because they allow self-renewal to occur: The exponential growth of the progenitors of AML cultured in suspension is due to self-renewal. METHODS AND MATERIALS: Cells were harvested from previously untreated leukemic human bone marrows. The myeloblastic lineage of the colonies was assessed by morphological, cytochemical, and immunophenotypic analysis, and by the use of growth factors that did not stimulate the growth of T-lymphocytes. The cell-cycle distribution of the blasts was analyzed by flow cytometry and was comparable for all samples. The irradiation was performed with gamma-photons at a dose-rate of 0.05 Gy/min, similar to the clinical conditions used in our institution for total body irradiation (TBI). RESULTS: The culture methods selected aggressive leukemias. There were large variations of the individual radiosensitivity whatever culture method was used. The progenitor cells capable of self-renewal were more radiosensitive than terminal dividing cells. In two cases, a shoulder was found in the initial part of the cell-survival curves of cells capable of self-renewal. In these two cases, the best fit for the data was the linear quadratic model (survival = e-alpha D-beta D2) with alpha/beta values of 1.49 Gy and 3.12 Gy, respectively. CONCLUSION: The very low values of alpha/beta suggest a reduced antileukemic effect in case of fractionated TBI, and may lead to more reliable screening methods to determine the most appropriate technique for radiation ablation of bone marrow prior to bone marrow transplantation (BMT).
Assuntos
Medula Óssea/efeitos da radiação , Células-Tronco Hematopoéticas/efeitos da radiação , Leucemia Mieloide Aguda/patologia , Adolescente , Adulto , Idoso , Crise Blástica , Medula Óssea/patologia , Ciclo Celular/efeitos da radiação , Diferenciação Celular , Divisão Celular/efeitos da radiação , Sobrevivência Celular/efeitos da radiação , Técnicas de Cultura/métodos , Relação Dose-Resposta à Radiação , Feminino , Citometria de Fluxo , Raios gama , Células-Tronco Hematopoéticas/patologia , Humanos , Masculino , Metilcelulose , Pessoa de Meia-Idade , Fótons , Células Tumorais CultivadasRESUMO
Helper T cells and suppressor T cells have been generated in vitro that regulate the cytolytic T lymphocyte (CTL) response to trinitrophenyl (TNP)-modified syngeneic cells. B6D2F1 helper cells generated to TNP-modified parental (P1) cells augment the CTL response to those P1-TNP-modified antigens but not to P2-TNP-modified antigens. The generation of these helper T cells requires the presence of splenic adherent cells and these helper T cells are radioresistant. A soluble factor can be obtained from the helper T cell cultures that can also augment the CTL response. The suppressor T cells generated in culture do not demonstrate the specificity observed with the helper T cells; however, they are antigen-dependent in their induction. Whether helper or suppressor activity is obtained depends upon the length of time cells are cultured in vitro.
Assuntos
Citotoxicidade Imunológica , Nitrobenzenos/imunologia , Linfócitos T Reguladores/imunologia , Linfócitos T/imunologia , Trinitrobenzenos/imunologia , Animais , Adesão Celular , Células Cultivadas , Cruzamentos Genéticos , Interleucina-1 , Cinética , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos DBA , Biossíntese de Proteínas , Baço/citologia , Linfócitos T/citologia , Linfócitos T/efeitos da radiação , Linfócitos T Reguladores/citologiaRESUMO
The cytokine human interleukin for Da cells/leukemia inhibitory factor (HILDA/LIF) exerts multiple biological effects in vitro. In mice, high circulating levels of HILDA/LIF induce a wide range of pathophysiological events, some of them closely involved with immunological and inflammatory responses. Using a sandwich ELISA recognizing the natural human HILDA/LIF molecule with a threshold of 50 pg/ml in urine and 150 pg/ml in plasma, we monitored the urine and plasma HILDA/LIF levels of 22 patients in their first year after a kidney transplant. HILDA/LIF urine excretion is increased during acute rejection, and infections also trigger heavy HILDA/LIF plasma concentrations or urine excretion. In addition, this study raises the question of HILDA/LIF involvement in post-kidney-transplant phenomena such as hypercalcemia, osteoporosis, or the reversal of anemia.
Assuntos
Inibidores do Crescimento/sangue , Inibidores do Crescimento/urina , Interleucina-6 , Transplante de Rim/fisiologia , Linfocinas/sangue , Linfocinas/urina , Adolescente , Adulto , Anuria/etiologia , Feminino , Rejeição de Enxerto , Humanos , Transplante de Rim/efeitos adversos , Transplante de Rim/imunologia , Fator Inibidor de Leucemia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Procedimentos Cirúrgicos Operatórios , Fatores de TempoRESUMO
Recently, a new lymphokine called HILDA (human interleukin for DA cells) has been described and cloned. This cytokine, initially described to be produced by alloreactive T lymphocyte clones grown from a rejected human kidney allograft, is identical to other factors termed D-factor, differentiation-inducing factor, differentiation inhibitory activity, hepatocyte-stimulating factor III, and leukemia inhibitory factor. HILDA/LIF induces various effects on neural, hemopoietic, embryonic cells as well as on bone remodeling and acute phase protein synthesis in hepatocyte. In this study we demonstrate the presence of HILDA/LIF in the urine but not in the serum of kidney graft recipients during acute rejection episodes, whereas this lymphokine was detectable neither in the serum nor in the urine of kidney transplanted patients with stable renal function. These data reinforce the notion of a possible role for this lymphokine in the inflammatory and/or the immune response.
Assuntos
Inibidores do Crescimento/urina , Interleucina-6 , Transplante de Rim/imunologia , Linfocinas/urina , Anticorpos Monoclonais/uso terapêutico , Creatinina/sangue , Feminino , Rejeição de Enxerto , Inibidores do Crescimento/sangue , Humanos , Imunossupressores/uso terapêutico , Rim/fisiologia , Fator Inibidor de Leucemia , Linfocinas/sangue , Masculino , Metilprednisolona/uso terapêuticoRESUMO
We have investigated the role of prostaglandin E2 (PGE2) in the regulation of cytokine release (IL-2, IL-3 and IFN) by cortico-resistant thymocytes (CRT) stimulated or not through the T-cell antigen receptor by an anti-CD3 monoclonal antibody (mAb). CRT were found to spontaneously produce IL-2 and IL-3 on day 4 of culture, but not IFN. After activation with an anti-CD3 mAb, the maximal levels for IL-2 and IFN were observed on day 1 and for IL-3 on day 4. Addition of PGE2 inhibits IL-2 production and has no effect on IFN production. Indomethacin, an inhibitor of the cyclooxygenase pathway, enhanced both IL-2 and IFN production. In contrast, IL-3 secretion by anti-CD3 activated CRT was up-regulated by PGE2, and its level was decreased in the presence of indomethacin in both stimulated or unstimulated cells. As has been observed with PGE2, forskolin which activates adenylate cyclase increases the IL-3 level. Thus PGE2 may interfere in the process of thymocyte proliferation and/or differentiation by regulating differentially the interleukin production.
Assuntos
Citocinas/metabolismo , Dinoprostona/fisiologia , Timo/imunologia , Animais , Anticorpos Monoclonais , Complexo CD3/imunologia , Células Cultivadas , Feminino , Hidrocortisona/fisiologia , Interferons/metabolismo , Interleucina-2/metabolismo , Interleucina-3/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Timo/citologiaRESUMO
PGE2 is produced by cells of the thymic microenvironment. The effects of PGE2 are mediated by cAMP through binding to its intracellular receptor protein kinase A (PKA). Phorbol 12-myristate 13-acetate (PMA) is known to modulate CD molecule expression on thymocytes, probably through activation of protein kinase C (PKC). We have hypothesized that cross-talk between these two signalling pathways may affect modulation of the CD molecules on the cell surface of thymocytes. For this purpose, we compare the effects of PMA alone or combined with PGE2 on CD3, CD4 and CD8 expression on mouse thymocytes by flow-cytometric analysis. PMA treatment almost completely abolished CD4 expression and slightly decreased CD3 and CD8 expression. PGE2 alone did not change the CD3, CD4 and CD8 molecule expression. Combined with PMA, PGE2 can overcome the decrease induced by PMA of the CD3 expression and partially reduced the disappearance of the CD4 molecule. On the other hand PGE2 accelerated the loss of CD8 molecule expression. These events occurred only in CD4+ CD8+ immature thymocytes. An analogue of cAMP (dibutyryl cAMP) mimics the effect of PGE2, but not Br-cGMP. This differential regulation by PGE2 of the CD molecule expression on immature thymocytes may provide additional evidence on the role of PGE2 during the process of thymic differentiation.
Assuntos
Antígenos CD/biossíntese , Dinoprostona/farmacologia , Linfócitos T/efeitos dos fármacos , Linfócitos T/imunologia , Acetato de Tetradecanoilforbol/farmacologia , Animais , Bucladesina/farmacologia , Complexo CD3/biossíntese , Antígenos CD4/biossíntese , Antígenos CD8/biossíntese , Células Cultivadas , GMP Cíclico/análogos & derivados , GMP Cíclico/farmacologia , Dinoprosta/farmacologia , Feminino , Citometria de Fluxo , Camundongos , Camundongos Endogâmicos C57BL , Prostaglandina D2/farmacologia , Propriedades de Superfície , Timo/citologia , Timo/efeitos dos fármacosRESUMO
Leukemia Inhibitory Factor (LIF) has a wide variety of biological activities. It regulates the differentiation of embryonic stem cells, neural cells, osteoblasts, adipocytes, hepatocytes and kidney epithelial cells. It also triggers the proliferation of myoblasts, primordial germ cells and some endothelial cells. Many of these biological functions parallel those of interleukin-6, Oncostatin M, ciliary neurotrophic factor, interleukin-11 and cardiotrophin-1. These structurally related cytokines also share subunits of their receptors which could partially explain the redundancy in this system of soluble mediators. In vivo LIF proves important in regulating the inflammatory response by fine tuning of the delicate balance of at least four systems in the body, namely the immune, the hematopoietic, the nervous and the endocrine systems. Although we are far from its therapeutic applications, the fast increasing knowledge in this field may bring new insights for the understanding of the cytokine biology in general.
Assuntos
Inibidores do Crescimento/fisiologia , Interleucina-6 , Linfocinas/fisiologia , Animais , Humanos , Fator Inibidor de Leucemia , Subunidade alfa de Receptor de Fator Inibidor de Leucemia , Camundongos , Estrutura Molecular , Receptores de Citocinas/fisiologia , Receptores de OSM-LIFRESUMO
The effects of prostaglandin E2 (PGE2) have been studied on a highly purified population of murine IL-2 activated killer cells obtained by selecting plastic-adherent splenocytes (AK cells) after incubation with high doses of recombinant IL-2. AK cells were highly cytotoxic for YAC-1 target cells. The cytotoxic activity was detectable at one hour after initiation of the cytotoxic assay and then increased with time. Cytotoxic activity of AK cells was inhibited by the addition of PGE2 or forskolin during the cytotoxic assay. When AK cells were generated in the presence of PGE2, the yielding cytotoxic activity was lower than the one expressed by "regular" AK cells but were insensitive to the inhibitory effect of PGE2 even if their lytic capability was still suppressed by forskolin. The presence of PGE2 during the AK cell culture had no effect on the cellular proliferation. Moreover, using tetrazolium-based colorimetric assay which reflects the cellular activation, it was observed that AK cells cultured in presence of PGE2 had an increased capacity to cleave the tetrazolium salt to formazan. Since the cytotoxic activity of killer cells is related to expression of serine esterase enzymes we evaluated the effects of PGE2 on serine esterase (Granzyme A) release after one hour of incubation of AK cells either alone or in presence of PGE2, YAC-1 cells or both. We observed that (i) AK cells spontaneously release granzyme A, (ii) the level of granzyme A was significantly increased when AK cells were incubated either with YAC-1 cells or PGE2 but did not change when YAC-1 cells and PGE2 were both associated with AK cells.
Assuntos
Citotoxicidade Imunológica/efeitos dos fármacos , Dinoprostona/farmacologia , Células Matadoras Ativadas por Linfocina/efeitos dos fármacos , Serina Endopeptidases/efeitos dos fármacos , Animais , Imunofluorescência , Granzimas , Interleucina-2/fisiologia , Células Matadoras Ativadas por Linfocina/enzimologia , Células Matadoras Ativadas por Linfocina/imunologia , Camundongos , Camundongos Endogâmicos C3H , Serina Endopeptidases/biossíntese , Células Tumorais CultivadasRESUMO
The relationship between immune activation and the development of early depressive symptoms were studied in 33 cancer patients undergoing cytokine therapy. Patients were treated either with subcutaneous IL-2 administered alone (n=13) or in association with IFN-alpha (n=5), or with IFN-alpha alone administered subcutaneously at low doses (n=5) or intravenously at high doses (n=10). The intensity of depressive symptoms was assessed during a clinical interview carried out before the start of cytokine therapy and five days later using the Montgomery and Asberg Depression Rating Scale (MADRS). On the same days, blood samples were collected for each patient to measure serum concentrations of cytokines (IL-6, IL-10, IL-1ra) and cytokine-receptors (sIL-2R, LIF-R). Results showed that patients treated with IL-2 or IL-2+IFN-alpha displayed concomitant mood symptoms and increased serum cytokine levels during treatment. In these patients, the intensity of depressive symptoms at endpoint was positively correlated with the increases measured in serum levels of IL-10 between baseline and endpoint. IL-10 is an anti-inflammatory cytokine that is produced in response to the production of pro-inflammatory cytokines, and thereby reflects an inflammatory response. These results support the hypothesis of close relationship between depressive symptoms and the activation of the cytokine network.
Assuntos
Carcinoma de Células Renais/tratamento farmacológico , Carcinoma de Células Renais/imunologia , Depressão/induzido quimicamente , Depressão/psicologia , Imunidade/efeitos dos fármacos , Interleucina-2/efeitos adversos , Interleucina-2/uso terapêutico , Neoplasias Renais/tratamento farmacológico , Neoplasias Renais/imunologia , Afeto , Idoso , Carcinoma de Células Renais/psicologia , Citocinas/sangue , Feminino , Humanos , Interferon-alfa/uso terapêutico , Neoplasias Renais/psicologia , Masculino , Pessoa de Meia-IdadeRESUMO
Since there is a good deal of evidence that vicia villosa lectin (VVA) binds to contrasuppressor cells, mouse splenocytes and thymocytes were sorted by binding to VVA-coated Petri dishes. It was observed that vicia villosa adherent cells (VVA(+)) did not proliferate when mitogens were added to cultures, but they did enhance the thymidine uptake of PHA or ConA stimulated vicia villosa non-adherent (VVA(-)) splenocytes. PGE2 treatment of VVA(+) splenocytes or VVA(+) immature thymocytes did not very much affect the VVA(+) cell behavior. On the other hand, LTB4 increased the enhancing capability of VVA(+) splenocytes. Therefore, investigations dealing with the effects of LTB4 on lymphocyte subsets which may include VVA(+) cells should take into consideration the possible presence of contrasuppressor cells.
Assuntos
Lectinas/metabolismo , Leucotrieno B4/análogos & derivados , Linfócitos/efeitos dos fármacos , Lectinas de Plantas , Prostaglandinas E/farmacologia , Animais , Dinoprostona , Feminino , Ativação Linfocitária/efeitos dos fármacos , Linfócitos/classificação , Linfócitos/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Baço/citologia , Timo/citologiaRESUMO
OBJECTIVE: Leukaemia inhibitory factor (LIF) is a polyfunctional cytokine integrated in cytokine networks and its concentration has been shown to be elevated in bronchoalveolar lavage fluid of patients with the acute respiratory distress syndrome (ARDS). The aim of our study was to evaluate the production of LIF by culturing blood cells from patients with ARDS. PATIENTS: 8 patients with ARDS, 8 patients with pneumonia and 5 healthy subjects. MEASUREMENTS AND RESULTS: The blood samples were taken on day 1 after onset of ARDS. LIF was measured, in the cell-free supernatant, with an enzyme-linked immunosorbent assay after 24 h, 48 h and 72 h of blood cell culture. LIF was detectable in some patients in the ARDS group: at i) at 24 h and 48 h: in 2 patients ii) at 72 h in 4/5 patients (140 +/- 231 pg/ml). Only in the 4 patients in whom LIF was measured at 72 h was ARDS associated with the multiple organ dysfunction syndrome. Furthermore, among the 5 patients with ARDS who subsequently died, 4 had a detectable LIF. CONCLUSIONS: We have observed that LIF was produced only in ARDS, but not in all patients. The production of LIF seems to be a good indicator of the severity of ARDS. These preliminary results must be confirmed by a larger study.
Assuntos
Inibidores do Crescimento/sangue , Interleucina-6 , Linfocinas/sangue , Síndrome do Desconforto Respiratório/sangue , Síndrome do Desconforto Respiratório/imunologia , Idoso , Estudos de Casos e Controles , Técnicas de Cultura de Células , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Fator Inibidor de Leucemia , Masculino , Pessoa de Meia-Idade , Insuficiência de Múltiplos Órgãos/etiologia , Pneumonia/sangue , Pneumonia/imunologia , Estudos Prospectivos , Síndrome do Desconforto Respiratório/complicações , Síndrome do Desconforto Respiratório/mortalidade , Fatores de TempoRESUMO
Eicosanoids have been shown to be potent immunoregulatory arachidonic acid (AA) metabolites. AA is the precursor of prostaglandin E(2) (PGE(2)) and leukotriene B(4) (LTB(4)) which are able to modulate both inflammation and the immune response. Dendritic cells process and present antigens to T lymphocytes. They are highly specialized antigen-presenting cells (APC) and usually considered as 'professional APC'. In the present paper, we report some data on the biosynthetic capacity of murine APC from the bone marrow (BM-DCs) to produce AA metabolites. Using an ELISA we have observed that BM-DCs spontaneously produce both PGE(2) and LTB(4) whose production increased in response to bacterial lipopolysaccharides (LPS). In addition we found that LTB(4) production was twice as high when both COX pathways were blocked with selective COX-inhibitors. We have also investigated the effect of PGE(2) and LTB(4) on the in vitro generation of the so-called BM-DCs. Exogenous PGE(2) and LTB(4) added to bone marrow cultures inhibit and promote, respectively, BM-DC generation. PGE(2) added to the maturing BM-DCs reduces their MHC class-II expression.
Assuntos
Apresentação de Antígeno/imunologia , Células Dendríticas/imunologia , Dinoprostona/imunologia , Leucotrieno B4/imunologia , Animais , Células da Medula Óssea/imunologia , Células da Medula Óssea/metabolismo , Antígeno CD11c/biossíntese , Células Cultivadas , Intervalos de Confiança , Inibidores de Ciclo-Oxigenase/farmacologia , Citocinas/biossíntese , Células Dendríticas/efeitos dos fármacos , Células Dendríticas/metabolismo , Dinoprostona/biossíntese , Regulação para Baixo , Ensaio de Imunoadsorção Enzimática , Feminino , Citometria de Fluxo , Antígenos de Histocompatibilidade Classe II/biossíntese , Leucotrieno B4/biossíntese , Camundongos , Camundongos Endogâmicos BALB C , FenótipoRESUMO
The present review deals with the role(s) of thymus-eicosanoids in the immune response. It reports the production of cyclooxygenase and lipoxygenase metabolites of arachidonic acid by cells of the thymus microenvironment and the role(s) of these eicosanoids in the differentiation and the maturation of immature T-cells. The possibility that these products may be involved in tolerance to self is discussed. Briefly, it is likely that cells from the monocyte-macrophage lineage which constitute a part of the thymus microenvironment could contribute to the education of immature thymocytes by both presenting self-antigens and producing eicosanoids. Tolerance to self might result from PGE2-driven apoptosis and/or LTB4-induced generation of suppressor cells.
Assuntos
Eicosanoides/fisiologia , Timo/fisiologia , Animais , Bovinos , Humanos , Camundongos , RatosRESUMO
A model of in vivo secondary graft-versus-host (GVH) was used to appraise the behaviour of allostimulated eicosanoid-treated thymocytes. During the first step of the experiment P1 immature parental thymocytes were preincubated in the presence of P2 allogenic mature lymphocytes and eicosanoids (either PGE2 or LTB4). During the second step, the preincubated cells were injected intravenously into P1xP2 F1 irradiated hybrids and the in vivo mixed lymphocyte reaction assessed by 3H-thymidine uptake by the cells harboured in the spleen of the host. We also investigated the production of cytotoxic cells. We observed that PGE2 and LTB4 both influence the behaviour of immature thymocytes and that, in the context of allostimulation such as GVH, they induce a state of tolerance. The data are in agreement with a model of involvement of eicosanoids in education of thymocytes within the thymic organ.
Assuntos
Eicosanoides/farmacologia , Reação Enxerto-Hospedeiro/efeitos dos fármacos , Timo/fisiologia , Animais , Divisão Celular/efeitos dos fármacos , Divisão Celular/imunologia , Células Cultivadas , Técnicas de Cocultura , Testes Imunológicos de Citotoxicidade , Dinoprostona/farmacologia , Feminino , Reação Enxerto-Hospedeiro/imunologia , Tolerância Imunológica/efeitos dos fármacos , Leucotrieno B4/farmacologia , Teste de Cultura Mista de Linfócitos , Linfócitos/imunologia , Camundongos , Timidina/metabolismoRESUMO
15-HETE is an arachidonic acid derivative issued from the 15 lipoxygenase pathway. This fatty acid possesses immunomodulatory capabilities since it was reported that it generates CD8 + suppressor T-cells either in vitro or ex vivo. The aim of the present report was to study if the suppressive capabilities of 15-HETE were able to influence the onset of the NZB/NZW Fl auto-immune disease. For that purpose we produced 15-HETE and injected the eicosanoid twice a week to NZB/WFI mice for 40 weeks. During the 15-HETE treatment of the animals it was observed an augmentation of the proliferative response of lectin-stimulated splenocytes (at weeks 20 and 30) then the thymidine uptake decreased (at week 40). In fact we observed that among 15-HETE treated mice the evolution of the nephropathy was not changed, the 'glomerular activity score' remained the same for the treated animals compared to controls. On the contrary antinuclear antibodies occurred earlier even if in some experiments the generation of CD8 + cells was demonstrated.
Assuntos
Doenças Autoimunes/tratamento farmacológico , Ácidos Hidroxieicosatetraenoicos/uso terapêutico , Nefrite Lúpica/tratamento farmacológico , Ativação Linfocitária/efeitos dos fármacos , Animais , Autoanticorpos/biossíntese , Doenças Autoimunes/imunologia , Doenças Autoimunes/prevenção & controle , Feminino , Ácidos Hidroxieicosatetraenoicos/farmacocinética , Ácidos Hidroxieicosatetraenoicos/farmacologia , Nefrite Lúpica/imunologia , Nefrite Lúpica/prevenção & controle , Masculino , Camundongos , Camundongos Endogâmicos BALB C/metabolismo , Camundongos Endogâmicos NZB/imunologia , Fatores Sexuais , Linfócitos T Reguladores/efeitos dos fármacos , Linfócitos T Reguladores/imunologiaRESUMO
Evolution of some immunological parameters was observed during the first month in 20 patients with different abdomino-pelvic cancers who underwent surgery with intra-operative radiation therapy (IORT) (mean dose of 19.44 Gy, range 15, 25). Observed parameters before (DO-) and after procedure (DO+), on seventh (D7) and fourteenth (D14) days and fifth week (D30) were: lymphocyte count, lymphocyte subsets (CD19, CD3, CD4, CD8, CD56), natural killer (NK) activity, immunoglobulins, C3 and C4b fractions of complement, soluble receptor for interleukin 2 (sIL2-R). Results showed a decrease of circulating lymphocytes (DO-: 1189 +/- 168 cells/mm3; D7: 889 +/- 91; P = 0.011), of absolute number of CD3 lymphocytes (DO-: 785 +/- 114 cells/mm3; D7: 563 +/- 86; P = 0.025), of CD4 lymphocytes (DO-: 441 +/- 70 cells/mm3; DO+: 299 +/- 43; P = 0.013) and of CD8 lymphocytes (DO-:361 +/- 50 cells/mm3, D7:250 +/- 44; P = 0.006). All values returned towards preoperative levels by D30. Absolute number of NK cells was unchanged but NK activity was significantly diminished (effector target ratio 5:1 DO-:33 +/- 5%; DO+:44 +/- 7%; D7:18 +/- 3%; D14:21 +/- 4%; D30:25 +/- 4%). sIL2-R was significantly enhanced from D7 to D30. All these impairments are moderate and these observations provide some evidence of satisfactory tolerance to IORT for abdomino-pelvic cancers during the immediate postoperative period.
Assuntos
Neoplasias Abdominais/radioterapia , Neoplasias Pélvicas/radioterapia , Neoplasias Abdominais/imunologia , Neoplasias Abdominais/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Terapia Combinada , Citotoxicidade Imunológica/efeitos da radiação , Feminino , Humanos , Tolerância Imunológica/efeitos da radiação , Cuidados Intraoperatórios , Células Matadoras Naturais/imunologia , Células Matadoras Naturais/efeitos da radiação , Subpopulações de Linfócitos/efeitos da radiação , Masculino , Pessoa de Meia-Idade , Neoplasias Pélvicas/imunologia , Neoplasias Pélvicas/cirurgia , Período Pós-Operatório , Receptores de Interleucina-2/metabolismo , SolubilidadeRESUMO
The authors present detailed data about skin fibrosis appearing in hyperthyroidism treated by Sotalol and radioactive iodine. Cutaneous thickening is discovered quite rapidly when the patient is monitored daily (as in case 4). It is asymptomatic and no other features of scleroderma are found. Regression occurs within 4-10 months. Histologically, fibrosis is located in the entire dermis. Dermal appendages are normal and no inflammatory changes occur. No anomalies of collagen structure and fibroblasts have been observed ultrastructurally. Immunological studies (direct immunofluorescence of the skin, lymphocyte transformation and leucocyte migration tests with Sotalol) were normal. The mechanism is unknown, but an immunological or a toxic one is excluded; however a pharmacological action is possible. The role of other betablockers must be assessed by a randomised study.