RESUMO
A 26-year-old Japanese woman developed autoimmune pulmonary alveolar proteinosis (PAP) during glucocorticoid therapy for systemic lupus erythematosus (SLE). Intensive immunosuppressive therapy worsened the PAP. De-escalation of immunosuppressive therapy improved the PAP. Autoimmune PAP is rarely associated with systemic autoimmune diseases, and the present case is the first case of autoimmune PAP associated with SLE. Moreover, the present case suggests that immunosuppressive therapy should be avoided or used carefully for the treatment of patients with anti-GM-CSF antibody, such as those with autoimmune PAP.
Assuntos
Doenças Autoimunes/etiologia , Imunossupressores/efeitos adversos , Lúpus Eritematoso Sistêmico/complicações , Proteinose Alveolar Pulmonar/etiologia , Adulto , Autoanticorpos/sangue , Feminino , Fator Estimulador de Colônias de Granulócitos e Macrófagos/imunologia , Humanos , Lúpus Eritematoso Sistêmico/tratamento farmacológicoRESUMO
Invariant natural killer T (iNKT) cells are considered innate-like lymphocytes, and regulate the immunity against inflammation and tumorigenesis. However, the impact of iNKT cells in inflammation-associated tumorigenesis remains unclear. In this study, we examined the physiological role of iNKT cells in a mouse colitis-associated colorectal cancer model. C57BL/6 (B6) and Jα18 NKT cell-deficient KO (KO) mice were used. Colitis-associated colorectal cancer was induced by azoxymethane (AOM) and dextran sodium sulfate (DSS). The resulting inflammation and tumours were examined. The surface markers of mononuclear cells from the liver and the colon were assessed by FACS. The levels of IL-13 from the colon were measured by ELISA. α-galactosylceramide (GC), or its close analog OCH, was administered intraperitoneally on the first day of each cycle of DSS-administration. In the AOM/DSS model, hepatic iNKT cells were significantly decreased. In KO mice there were significantly greater numbers of colon tumours and more severe inflammation than in B6 mice. FACS analysis revealed that the population of NK1.1 (+) T cells (non-invariant NKT cells) in the colon was increased when compared to B6 mice. The secretion of IL-13 was increased in the colon of KO mice after AOM/DSS. The number of colon tumours was significantly decreased in the GC-treated group compared to the control group. GC-treatment significantly inhibited IL-13 secretion from the colonic mononuclear cells and the number of colonic NK1.1 (+) T cells was significantly decreased. These results suggest that iNKT cells may play a critical role in the prevention of tumour progression and inflammation in the AOM/DSS model.
Assuntos
Colite/imunologia , Neoplasias Colorretais/imunologia , Células T Matadoras Naturais/imunologia , Animais , Modelos Animais de Doenças , Citometria de Fluxo , Galactosilceramidas/imunologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Organismos Livres de Patógenos EspecíficosRESUMO
Ganoderma lucidum Karst is well known as 'Reishi', a traditional food in China and Japan. It contains a polysaccharide component known to induce granulocyte macrophage colony-stimulating factor (GM-CSF) production from murine splenocytes. Moreover, GM-CSF may be a therapeutic agent for Crohn's disease. In this study, we investigated the water-soluble, polysaccharide components of Reishi (designated as MAK) in murine colitis induced by trinitrobenzene sulphonic acid (TNBS). We examined the concentration of GM-CSF in peritoneal macrophage cells (PMs) of C57BL/6 mice during in vitro and in vivo stimulation with MAK. After feeding with chow or MAK for 2 weeks, 2 mg of TNBS/50% ethanol was administered to each mouse. After 3 days of TNBS treatment, intestinal inflammation was evaluated, and mononuclear cells of the mesenteric lymph nodes (MLNs) and colon were cultured for ELISA. To determine the preventive role of GM-CSF, the mice were pre-treated with or without anti-GM-CSF antibody before TNBS administration. In vitro and in vivo MAK-stimulated PMs produced GM-CSF in a dose-dependent manner. Intestinal inflammation by TNBS was improved by feeding with MAK. MLNs of mice treated with TNBS produced IFN-γ, which was inhibited by feeding with MAK. In contrast, MLNs of mice treated with TNBS inhibited GM-CSF production, which was induced by feeding with MAK. The colon organ culture assay also revealed that IFN-γ was decreased and GM-CSF was increased by MAK. The preventive effect was blocked by the neutralization of GM-CSF. We concluded that the induction of GM-CSF by MAK may provide the anti-inflammatory effect.
Assuntos
Colite/tratamento farmacológico , Colo/efeitos dos fármacos , Macrófagos Peritoneais/efeitos dos fármacos , Micélio/metabolismo , Reishi/imunologia , Animais , Anti-Inflamatórios/administração & dosagem , Anticorpos Monoclonais/administração & dosagem , Células Cultivadas , Colite/induzido quimicamente , Colite/patologia , Colite/fisiopatologia , Colo/imunologia , Colo/patologia , Meios de Cultura/metabolismo , Modelos Animais de Doenças , Medicamentos de Ervas Chinesas/administração & dosagem , Fator Estimulador de Colônias de Granulócitos e Macrófagos/imunologia , Fator Estimulador de Colônias de Granulócitos e Macrófagos/metabolismo , Humanos , Interferon gama/genética , Interferon gama/metabolismo , Macrófagos Peritoneais/imunologia , Macrófagos Peritoneais/metabolismo , Macrófagos Peritoneais/patologia , Camundongos , Camundongos Endogâmicos C57BL , Micélio/crescimento & desenvolvimento , Ácido Trinitrobenzenossulfônico/administração & dosagemAssuntos
Proteínas ADAM/sangue , Doenças do Tecido Conjuntivo/sangue , Inibidores de Proteases/sangue , Púrpura Trombocitopênica Trombótica/sangue , Fator de von Willebrand/análise , Proteínas ADAM/antagonistas & inibidores , Proteína ADAMTS13 , Adulto , Idoso , Idoso de 80 Anos ou mais , Autoanticorpos/sangue , Doenças do Tecido Conjuntivo/complicações , Doenças do Tecido Conjuntivo/epidemiologia , Feminino , Humanos , Japão/epidemiologia , Pessoa de Meia-Idade , Púrpura Trombocitopênica Trombótica/complicações , Púrpura Trombocitopênica Trombótica/epidemiologiaRESUMO
Two types of 4-methylpyridinium polymers (4VP-DVB-Me and 4VP-EG-Me, cross-linked with divinylbenzene and ethylene glycol dimethacrylate, respectively) were employed for the analysis of proteins in ion-exchange high-performance liquid chromatography. These polymers had different physical properties in the dry state, but showed similar retentions in size-exclusion chromatography using carbohydrate standards. Generally, the 4VP-EG-Me column was superior to the 4VP-DVB-Me column with regard to separation and recovery of proteins.
Assuntos
Cromatografia Líquida de Alta Pressão , Proteínas/análise , Polímeros , Compostos de Piridínio , Espectrofotometria UltravioletaRESUMO
OBJECTIVE: To examine the dose-specific effects of interleukin-12 (IL-12) on the evolution of murine type II collagen-induced arthritis (CIA). METHODS: From day 24 through day 33 following primary immunization, mice received daily intraperitoneal injections of murine recombinant IL-12. Measurements of anticollagen IgG, cytokines, and corticosterone were performed using enzyme-linked immunosorbent assay and radioimmunoassay. RESULTS: CIA mice injected with a low dose of IL-12 (5 ng/day) exhibited accelerated onset and increased severity of arthritis. In contrast, administration of a high dose of IL-12 (500 ng/day) attenuated arthritic inflammation. The low dose of IL-12 induced tumor necrosis factor alpha (TNFalpha) production, whereas the high dose induced production of both IL-10 and corticosterone and suppression of anticollagen antibody levels. Administration of neutralizing anti-TNFalpha and anti-IL-10 antibodies reversed the dose-specific effects of IL-12. CONCLUSION: IL-12 is an important immunomodulator during the pathogenesis of CIA. It appears to act by regulating humoral and cellular immune responses, as well as by mediating the expression of immunoregulatory cytokines and glucocorticoids.
Assuntos
Adjuvantes Imunológicos/farmacologia , Artrite Experimental/imunologia , Colágeno , Interleucina-12/imunologia , Animais , Anticorpos/análise , Anticorpos/uso terapêutico , Artrite Experimental/induzido quimicamente , Artrite Experimental/tratamento farmacológico , Colágeno/imunologia , Corticosterona/sangue , Relação Dose-Resposta Imunológica , Interleucina-10/biossíntese , Interleucina-10/genética , Interleucina-10/imunologia , Interleucina-12/farmacologia , Ativação Linfocitária/imunologia , Masculino , Camundongos , RNA Mensageiro/análise , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Baço/metabolismo , Fator de Necrose Tumoral alfa/biossínteseRESUMO
Abstract Various factors were assessed in terms of their contribution to arthralgia in a rheumatoid arthritis patient. Eighty-two outpatients (62 women and 20 men) with rheumatoid arthritis (RA) were examined with respect to the subjective degree of arthralgia, age, disease duration, dysfunction, steroid dose, steroid period, depression, anxiety, extroversion, neurotic disorder, and number of caretakers. The results were explained on the basis of stepwise regression analysis and psychological and clinical data. We analyzed results of a correlation coefficient test on the mutual relationship between variables. Stepwise regression analysis was performed to assess factors of arthralgia in terms of "depression," "mean activity," "morning stiffness," and "steroid dose." Depression is a factor of arthralgia as shown in this study, but it is clear that other factors are also involved. Anxiety was a factor distinct from the activity of RA. The factor contributing most to arthralgia was found to be depression, whereas anxiety had no effect.
RESUMO
OBJECTIVE: To study the effect of endothelin-1 (ET-1) on the expression of intercellular adhesion molecule-1 (ICAM-1) by synovial fibroblasts derived from individuals with rheumatoid arthritis (RA) or osteoarthritis (OA). METHODS: The expression of ICAM-1 protein and the abundance of ICAM-1 mRNA in synovial fibroblasts derived from individuals with RA or OA, or healthy controls, was assessed by flow cytometry and Northern blot analysis, respectively. mRNA expression of ET type A (ETA) and ET type B (ETB) receptors was assessed by reverse transcription polymerase chain reaction. RESULTS: Tumor necrosis factor-alpha (TNF-alpha) increased the expression of ICAM-1 by RA and OA fibroblasts. While ET-1 alone had no significant effect on ICAM-1 expression by either cell type, it inhibited the TNF-alpha induced increase in ICAM-1 expression, and this effect was more marked in RA fibroblasts. TNF-alpha also increased the amount of ICAM-1 mRNA in both cell types, and ET-1 inhibited this increase to a greater extent in RA fibroblasts than in OA fibroblasts. This inhibitory effect of ET-1 was reversed by addition of specific antagonist of ETA receptor. mRNA expression of ETA and ETB receptors was significantly greater in RA fibroblasts stimulated with TNF-alpha or even medium alone than in OA fibroblasts. CONCLUSION: These results suggest that ICAM-1 expression by fibroblasts is regulated not only by proinflammatory cytokines such as TNF-alpha and interleukin-1beta, but also by the vasoactive peptide ET-1, and that ET-1 may play an important role in inflammatory responses, especially in rheumatoid synovitis.
Assuntos
Endotelina-1/farmacologia , Fibroblastos/efeitos dos fármacos , Molécula 1 de Adesão Intercelular/biossíntese , Membrana Sinovial/efeitos dos fármacos , Idoso , Artrite Reumatoide/metabolismo , Células Cultivadas , Cicloeximida/farmacologia , Primers do DNA/química , Dactinomicina/farmacologia , Relação Dose-Resposta a Droga , Regulação para Baixo , Feminino , Fibroblastos/metabolismo , Citometria de Fluxo , Humanos , Técnicas Imunoenzimáticas , Molécula 1 de Adesão Intercelular/genética , Interleucina-1/farmacologia , Masculino , Pessoa de Meia-Idade , Osteoartrite/metabolismo , RNA Mensageiro/biossíntese , Receptor de Endotelina A , Receptor de Endotelina B , Receptores de Endotelina/genética , Receptores de Endotelina/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Membrana Sinovial/citologia , Membrana Sinovial/metabolismo , Fator de Necrose Tumoral alfa/farmacologiaRESUMO
OBJECTIVE: To determine the contribution made by synovial fluid (SF) neutrophils to the augmented expression of macrophage inflammatory protein 1 alpha (MIP-1alpha) in rheumatoid arthritis (RA). METHODS: Neutrophils were isolated from samples of SF from RA patients and peripheral blood (PB) samples from RA patients and healthy controls. Cell associated MIP-1alpha was visualised immunohistochemically, and cell associated MIP-1alpha as well as MIP-1alpha secreted into the SF was assayed by ELISA. Steady state expression of MIP-1alpha mRNA was assessed by reverse transcription polymerase chain reaction (RT-PCR). RESULTS: Freshly isolated SF neutrophils contained significantly higher concentrations of both MIP-1alpha protein and its transcript than PB neutrophils from either RA patients or healthy controls; incubation in the absence or presence of tumour necrosis factor alpha for 24 hours resulted in a significant increase in MIP-1alpha secretion by RA SF neutrophils compared with neutrophils obtained from either normal PB or RA PB; and expression of MIP-1alpha by SF neutrophils was well correlated with both RA disease activity and SF mononuclear cell (MNC) counts. CONCLUSION: Expression and secretion of MIP-1alpha by SF neutrophils may be indicative of local and systemic inflammation in RA. Moreover, this C-C chemokine may contribute to the recruitment of MNCs from the bloodstream into synovial joints and tissues.
Assuntos
Artrite Reumatoide/imunologia , Proteínas Inflamatórias de Macrófagos/análise , Neutrófilos/química , Líquido Sinovial/imunologia , Adulto , Idoso , Biomarcadores/análise , Quimiocina CCL3 , Quimiocina CCL4 , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Imuno-Histoquímica , Proteínas Inflamatórias de Macrófagos/genética , Masculino , Pessoa de Meia-Idade , RNA Mensageiro/análise , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Estatísticas não ParamétricasRESUMO
We described a case of rheumatoid arthritis (RA) with selective IgA deficiency. A 69 year-old female with RA was admitted because of gall bladder cancer, and also had selective IgA deficiency which serum IgA level was less than 5.0 mg/dl, and IgA 1 and IgA 2 subclasses were not detected. Prior to the operation, she was given red cell compatible blood transfusion because of severe anemia. After 30 min of transfusion, she developed chill, nausea, vomiting and hypotension. These anaphylactic reactions might be induced by the presence of anti-IgA antibody, since the level of this antibody titers in her serum was elevated, assessed by the methods of ELISA and Western blotting. Although a case of RA associated with selective IgA deficiency, and also with elevated serum anti-IgA antibody level is extremely uncommon, attention should be paid to the presence of anti-IgA antibody in patients with selective IgA deficiency to avoid any unexpected anaphylactic reactions.