Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0024141 (systemic lupus erythematosus)
 44,322 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The age-dependent capacity of NZB and (NZB x NZW)F1 hybrid, BALB/c, DBA/2, C57BL/6 and C3H mice to generate T cell-mediated immune responses was assessed qualitatively and quantitatively by measuring the following effector functions: (a) the time course of alloreactive cytotoxic T-cell activity triggered in vitro was comparable for NZ and other mouse strains; cell reactivity generated in vivo against EL4 tumour cells was low in young (NZB x NZW)F1 mice and in DBA/2 mice but was comparable for older (NZB x NZW)F1, NZB and other mouse strains; (b) the time-dependent, vaccinia virus-specific, cytotoxic T-cell activity after systemic infection was similar for all mouse strains; (c) the T cell-dependent primary footpad swelling after local injection with lymphocytic choriomeningitis virus was within the same range for all mouse strains tested with respect to size and kinetics of the reaction; (d) the cell-mediated immune protection against Listeria monocytogenes after systemic infection revealed that NZ mice are, independent of age, more susceptible than C3H or C57BL/6 mice and comparable to A strain mice. Therefore, these responses in young, or clinically relatively normal older, NZB or (NZB x NZW)F1 strains that are affected by a lupus-like autoimmune disease did not differ markedly from the range of responses of other mouse strains of 2-14 months of age, which are not known to be similarly diseased. Thus, overall cell-mediated immunity of NZ mice as assessed quantitatively and kinetically in these functional models is within normal ranges. Possible T-cell defects may therefore be selective and either do not occur or were not detected in these models.
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PMID:Comparison of T cell-mediated immune responsiveness of NZB, (NZB x &NZW)F1 hybrid and other murine strains. 14 94

Interleukin-2 (IL-2) is a T-cell derived molecule implicated in the clonal expansion of antigen-activated T cells and in T-cell development. IL-2 is also implicated in autoimmune disease, although its role is still controversial. Murine systemic lupus erythematosus (SLE) is a good model for human SLE as most of the immunological abnormalities in the human disease also seem to be operative in the mouse. Among SLE mice, the MRL/lpr strain develops early in life autoimmune diseases such as immune complex-mediated glomerulonephritis, arthritis and arteritis. Lymphoid abnormalities associated with those diseases in this strain are thymic atrophy and abnormal proliferation of CD3+ CD4- CD8- 'double-negative' T cells, resulting in massive generalized lymph node enlargement. We have therefore now examined the effects of IL-2 on the disease progression in MRL/lpr mice using live vaccinia recombinant viruses expressing the human IL-2 gene. Vaccinated mice showed prolonged survival, decreased autoantibody and rheumatoid factor titres, marked attenuation of kidney interstitial infiltration and intraglomerular proliferation, as well as clearance of synovial mononuclear infiltrates. Inoculation with the IL-2/vaccinia recombinant virus led, in addition, to drastic reduction of the double-negative T-cell population, improved thymic differentiation and restoration of normal values of mature cells in peripheral lymphoid organs.
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PMID:Recovery from autoimmunity of MRL/lpr mice after infection with an interleukin-2/vaccinia recombinant virus. 197 22

The principal cause of IL-2 deficiency, a common feature of both murine lupus and human SLE, remains obscure. Recent studies of our own as well as others have shown that dehydroepiandrosterone (DHEA), an intermediate compound in testosterone synthesis, significantly up-regulates IL-2 production of T cells, and that administration of exogenous DHEA or IL-2 via a vaccinia construct to murine lupus dramatically reverses their clinical autoimmune diseases. Thus, we have examined serum levels of DHEA in patients with SLE to test whether abnormal DHEA activity is associated with IL-2 deficiency of the patients. We found that nearly all of the patients examined have very low levels of serum DHEA. The decreased DHEA levels were not simply a reflection of a long term corticosteroid treatment which may cause adrenal atrophy, since serum samples drawn at the onset of disease, which are devoid of corticosteroid treatment, also contained low levels of DHEA. In addition, exogenous DHEA restored impaired IL-2 production of T cells from patients with SLE in vitro. These results indicate that defects of IL-2 synthesis of patients with SLE are at least in part due to the low DHEA activity in the serum.
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PMID:Low serum levels of dehydroepiandrosterone may cause deficient IL-2 production by lymphocytes in patients with systemic lupus erythematosus (SLE). 785 Oct 19

There is strong evidence to implicate the involvement of sex steroid hormones in the pathogenesis of systemic lupus erythematosus (SLE). However, the precise role of an imbalance of circulating sex hormones in the pathogenesis of the disease remains to be fully elucidated. Recent studies of our own as well as others have shown that dehydroepiandrosterone (DHEA), an intermediate compound in testosterone synthesis, significantly up-regulates IL-2 production of normal T cells and that administration of exogenous DHEA or IL-2 via a vaccinia construct to mice with murine lupus dramatically reverses their clinical autoimmune diseases. Thus, it is possible that in patients with SLE, the reported deficiency of IL-2 production is associated with defective DHEA activity. Indeed, we found that nearly all of the patients examined have very low levels of serum DHEA. The decreased DHEA levels are not simply a reflection of long term corticosteroid treatment, since serum samples drawn at the onset of disease, prior to any corticosteroid treatment also contained low levels of DHEA. In addition, supplementation with DHEA of the in vitro cultures of T cells restored impaired IL-2 production in patients with SLE. Thus, it would be suggested that defects of IL-2 synthesis in patients with SLE are at least in part due to the low DHEA activity in the serum, and that supplementation of DHEA could improve clinical manifestations in patients with SLE.
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PMID:Hormones and lupus: defective dehydroepiandrosterone activity induces impaired interleukin-2 activity of T lymphocytes in patients with systemic lupus erythematosus. 895 43