摘要:

The MRL/lpr model of SLE resembles human lupus in its various immunopathologic characteristics including the presence of high-level IgG and anti-DNA antibody production and multisystem organ involvement (nephritis, arthritis, and vasculitis). Our previous studies have shown that IL-1 overactivity in B cells plays a potentially important role in driving IgG and autoantibody production. However, the underlying mechanisms determining IL-1 overactivity are poorly understood. We studied IL-lβgene expression and transcriptional rates in B cells derived from old and young MRL/lpr, MRL/+ +, and non-autoimmune control mice using semi-quantitative RT-PCR and the nuclear run-on assay. RT-PCR demonstrated increased steady-state IL-lβgene expression in B cells derived from old MRL/lpr mice as compared to either young MRL/lpr or control mice. Furthermore, IL-lβgene expression in B cells was associated with the presence of the lpr mutation because heightened IL-1βmessage was observed in RNA obtained from MRL/lpr but not MRL/+ + B cells. IL-lβtranscriptional rates measured by the nuclear run-on assay were very similar in B cells from old and young MRL/lpr and control mice. These observations suggest that IL-1 overactivity in B cells obtained from old diseased MRL/lpr results from heightened IL-lβmessage, is associated with the presence of the lpr mutation, and is likely to reflect post-transciptional stabilization of IL-1βmRNA.

ISSN:0891-6934    

DOI:10.3109/08916939609001949

出版商:Taylor&Francis    

年代:1996

数据来源: Taylor

摘要:

Interferon-α(IFNα) has been shown to increase platelet numbers in patients with immune thrombocytopenic purpura (ITP), but the basis for this effect is not known. In this study changes in immune function were monitored following administration of IFNa to seven patients whose ITP had proved refractory to conventional therapy. Patients' peripheral blood mononuclear cells were cultured with phytohaemagglutinin and culture supernatants assayed for cytokine production. Production of the Thl cytokines IL-2 and IFN-γ/γwas low in patients compared to healthy controls, and amounts of these tended to increase after IFNβtherapy. In two patients high levels of IL-10 were detectable in culture, and these were reduced after IFNa. In patients who had high serum concentrations of IL-4 or IL-10, these were also decreased following therapy. Natural killer cell activity, which was low in the patients prior to therapy, was increased following administration of IFNβ. In those patients with detectable platelet-associated autoantibody to gpIIb/IIIa, the amounts were reduced after treatment. Two patients had an unusually high percentage of T cells expressing theγ/γ§T cell receptor, which decreased after therapy, The findings are consistent with an increase in Thl activity and a decrease in autoantibody production following IFNβtherapy, which may be related to the beneficial effects of this cytokine.

ISSN:0891-6934    

DOI:10.3109/08916939609001950

出版商:Taylor&Francis    

年代:1996

数据来源: Taylor

摘要:

We analysed inflammatory changes at selected time intervals, of salivary and lacrimal glands in the developing immunostimulatory [BN→(BN×LEW)Fl] model of graft-versus-host (GVH) reaction. A focal mononuclear adenitis in lacrimal and salivary glands developed at day 7 and increased clearly in“onset”-rats. Inflammatory responses in submandibular and parotid glands were less consistent and weaker than in lacrimal glands. There was no significant focus score difference between males and females.The lacrimal infiltrates were characterised immunohistochemically with monoclonal antibodies. Our findings indicate that CD4+cells of donor origin dominated infiltrates, whereas a moderate number of B cells appeared only in large (late) foci. At stages corresponding to the onset of GVH disease (GVHD) in skin/labial mucosa, numerous CD8+lymphocytes and NK cells were found in lacrimal glands, adjacent to ductal/vascular plexa, sometimes forming small foci and with evidence of epithelial damage.We conclude that GVHD-associated T cell migration into rat exocrine glands occurs as a result of the semi-alloantigen-activated phenotype properties of the T cells. This activation occurs initially in lymphoid tissue and migration into glands is secondary to this and unrelated to antigen specificity. We also found evidence of amplification and tissue damage, interpreted as due to local reactivation of the T cells.

ISSN:0891-6934    

DOI:10.3109/08916939609001951

出版商:Taylor&Francis    

年代:1996

数据来源: Taylor

摘要:

Environmental factors appear to be nongenetic risks of importance in the progression of insulin-dependent diabetes mellitus (IDDM) or type 1 diabetes, whose mechanisms are not yet well understood. Stressful life events, in particular, have been linked to the expression of overt diabetes in humans. However, in rodent models of IDDM, contradictory data exist concerning the effects of stress on the disease. Here, we show that a stressor, such as long-term repeated injections of vehicle (0.9% saline), was able to delay the appearance and/or decrease the incidence of diabetes in both sexes of NOD mice. Short-term chronic stress applied from the 6th to the 8th week of age by a combination of multiple stressors (overcrowding + immobilization + cold exposure + anesthesia) protected NOD mice from diabetes, particularly males. In contrast, prenatal stress, induced by immobilization of the mothers during the third part of pregnancy, accelerated the onset and increased the prevalence of diabetes at 30 weeks of age in NOD females, while it had no effect in males. Finally, adrenalectomy appears to aggravate the development of diabetes in NOD mice, particularly in males. In conclusion, these data demonstrate that the appearance of diabetes in NOD mice is extremely sensitive to various experimental and environmental conditions. These results are discussed in the context of the complex neuroendocrine-immune interactions which occur during the progression of IDDM, with a particular focus on glucocorticoids and cytokines.

ISSN:0891-6934    

DOI:10.3109/08916939609001952

出版商:Taylor&Francis    

年代:1996

数据来源: Taylor

摘要:

Antiphospholipid antibodies (APA) are a group of autoantibodies, including lupus anticoagulant (LA) and anticardiolipin antibodies (ACA), able to interfere with the coagulation system1. The presence of these autoantibodies has been related to the occurrence of arteriovenous thromboses, thrombocytopenia and fetal losses also in patients without diagnosis of systemic lupus erythematous (SLE)2. In order to reduce the pregnancy complications in patients with APA several prophylactic approaches have been proposed as successful treatment3,4. The majority of these prophylactic approaches had utilized intermediate- high dose prednisone and/or aspirin.

ISSN:0891-6934    

DOI:10.3109/08916939609001953

出版商:Taylor&Francis    

年代:1996

数据来源: Taylor

摘要:

We would like to provoke discussion on the standardization of experiments involving NOD mice, with a possible view to an international workshop on the subject at a future date.

ISSN:0891-6934    

DOI:10.3109/08916939609001954

出版商:Taylor&Francis    

年代:1996

数据来源: Taylor

ISSN:0891-6934    

DOI:10.3109/08916939609001955

出版商:Taylor&Francis    

年代:1996

数据来源: Taylor