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

While no one seems to doubt the importance of corticosteroids as potent anti-inflammatory and immunomodular agents, view about the dreaded complications are also rampant. There appears to be a wide variation in their use among various physicians depending on their individual beliefs, but generally there is a consensus in regard to their use in certain autoimmune/connective tissue disorders such as SLE, various vasculitides, etc., where no acceptable alternative medications exist. In these conditions relatively high doses of corticosteroids are needed until the disease activity is controlled and thereafter attempts should be made to taper down the dose to the lowest possible maintenance dose. In some situations such an attempt may not be successful because of exacerbation in disease activity. In such cases supplemental steroid sparing agents such as azathioprine and others should be considered. Other measures such as alternate day therapy should be considered if shown to be affective in controlling disease activity. Alternate day therapy has been shown to be associated with fewer side effects, notably HPA axis suppression, incidence of infection, myopathy and glucose intolerance. Pulsed i.v. Solumedrol has also been shown to be effective in certain situations such as rapidly progressive glomerulonephritis and renal transplant rejection. Steroids should not be used when an equally effective alternative medication is available such as NSAIDS and disease modifying agents in various inflammatory arthritis. Much of reported side effects in the literature are based on case reports and uncontrolled studies and there appears to be considerable individual variation in susceptibility. Some of the side effects are expected regardless of the size of the dose and cumulative dose whereas others are related to the dose. Certain side effects of steroids use, notably osteoporosis, have been shown to be significantly associated with long term use of corticosteroids whereas in others such as peptic ulcer disease, the association is tenuous with other variables playing a significant role. Potential for abuse/misuse also exists both by the physicians and patients. This, however, is relatively small here in the U.S. compared to developing countries where corticosteroids have been used irrationally and inappropriately in a wide variety of conditions, in high dosages.
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PMID:Uses, adverse effects of abuse of corticosteroids. Part I. 789 13

The level of platelet-associated IgG (PAIgG) is reported to be elevated in patients with systemic lupus erythematosus (SLE). However, the nature of PAIgG is unclear. We have investigated whether the PAIgG of SLE consists of anti-platelet autoantibodies or immune complexes (IC). The PAIgG values measured by flow cytometry were elevated in 11/25 patients with SLE. 3/6 SLE patients with thrombocytopenia had a high level of PAIgG (the mean fluorescence intensity > 10). We used an ether elution technique to determine whether elevated PAIgG consists of anti-platelet antibodies or IC. Preliminary experiments showed that the eluates prepared from platelets sensitized with anti-HPA-4a antibody reacted with normal platelets, while the eluates prepared from platelets sensitized with heat-aggregated IgG or model IC failed to react with normal platelets. These results indicate that the reactivity of eluates can distinguish between platelet-bound antibody and IC. We applied this technique to analysis of the PAIgG of SLE platelets. The eluates from SLE platelets (the mean fluorescence intensity > 10) reacted with normal platelets, indicating that the PAIgG of SLE platelets has the nature of antiplatelet autoantibodies. Furthermore, we investigated the target antigens which bind PAIgGs of SLE, using the direct immunoprecipitation procedure and modified antigen capture ELISA (MACE). Both methods identified GPIIb/IIIa as the target antigens. We conclude that the ether elution technique can distinguish between anti-platelet antibodies and IC, and that the PAIgGs of SLE with a high PAIgG value and thrombocytopenia have the nature of anti-platelet autoantibodies.
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PMID:Elevated platelet-associated IgG in SLE patients due to anti-platelet autoantibody: differentiation between autoantibodies and immune complexes by ether elution. 791 36

The levels of platelet-associated IgG (PAIgG) are reported to be elevated in patients with systemic lupus erythematosus (SLE). However, the nature of PAIgG is unclear. We investigated whether PAIgGs of SLE are anti-platelet autoantibodies or immune complexes (IC). PAIgG levels measured by flow cytometry in patients with SLE (n = 25) were 12.7 +/- 41.0 (expressed by mean channel), slightly high (but not significant) compared with healthy subjects (2.5 +/- 0.7). Three of 6 SLE patients with thrombocytopenia had high level of PAIgG (mean channels > 10). To determine whether elevated PAIgGs are composed of anti-platelet antibody or IC, we applied elution technique. Preliminary experiments showed that the eluate prepared form platelets sensitized with anti-HPA-4a antibody reacted with normal platelets, while the eluates prepared from platelets sensitized both with heat aggregated IgG and with model IC did not react with normal platelets. These results indicated that the reactivity of eluates could discriminate between platelet-bound antibody and IC. We applied this method for the analyses of PAIgG of SLE platelets. The eluates from SLE platelets (mean channels were more than 10) reacted with normal platelets, indicating that PAIgGs of SLE platelets are anti-platelet autoantibody, not IC. Furthermore, we investigated the target antigens which bound PAIgGs of SLE, using the direct immunoprecipitation and modified antigen capture ELISA (MACE). Both methods identified GPIIb/IIIa as target antigens. We concluded that 1) ether elution technique could differentiate between anti-platelet antibody and IC, 2) PAIgGs of SLE had a nature of anti-platelet autoantibody, 3) the target antigens of PAIgG were GPIIb/IIIa.
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PMID:[Anti-platelet antibodies in patients with autoimmune disorders]. 831 30

Hormones, particularly those involved in the hypothalamic-pituitary-gonadal and -adrenal axes (HPG and HPA), play important roles in various animal models of autoimmunity such as systemic lupus erythematosus in mice and collagen-induced arthritis (CIA) in mice and rats, and the streptococcal cell wall, adjuvant and avridine arthritis models in rats. Intimately linked to the subject of hormones and autoimmunity are gender, sex chromosomes and age. The importance of these factors in the various animal models is emphasized in this chapter. Several major themes are apparent. First, oestrogens promote B-cell dependent immune-complex mediated disease (e.g. lupus nephritis) but suppress T-cell dependent pathology (CIA in mice and rats), and vice versa. Second, testosterone's effects are complicated and depend on species and disease model. In rats, testosterone suppresses both T-cell and B-cell immunity. In mice, the effects are complex and difficult to interpret, e.g. they tend to enhance CIA arthritis and suppress lupus. Sex chromosome/sex hormone interactions are clearly involved in generating these complicated effects. Third, studies in Lewis and Fischer F344 rats exemplify the importance of corticosteroids, corticotrophin releasing hormone and the HPA axis in the regulation of inflammation and the predisposition to autoimmune diseases. Fourth, the HPA axis is intimately linked to the HPG axis and is sexually dimorphic. Oestrogens stimulate higher corticosteroid responses in females. The animal model data have major implications for understanding autoimmunity in humans. In particular, adrenal and gonadal hormone deficiency is likely to facilitate T-cell dependent diseases like rheumatoid arthritis, while high oestrogen levels or effects, relative to testosterone, are likely to promote B-cell dependent immune-complex-mediated diseases such as lupus nephritis.
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PMID:Hormones and autoimmunity: animal models of arthritis. 891 49

We have characterized the activation of the HPA axis in the chronic inflammatory stress model of adjuvant-induced arthritis. Alteration in the hypothalamic control mechanism, where CRF is no longer the major corticotrophin-releasing factor, has been noted in a number of other immune-mediated disease models, including experimental allergic encephalomyelitis, eosinophilia myalgia syndrome, systemic lupus erythematosus, and leishmaniasis. These changes occur in both the mouse and the rat, suggesting this may be a common mechanism to chronic immune activation. We have good evidence to suggest that AVP takes over as the major stimulator of the axis. The arthritic rat is unable to mount a response to acute stressors, such as restraint or ip hypertonic saline. However, these animals are able to mount a response to an acute immune challenge. These data provide further evidence for a differential activation of the HPA by acute stress or acute immune stimulation. This presumably reflects an adaptive response to the development of chronic inflammation. We have demonstrated that central neurotransmitter systems are able to influence the severity of peripheral inflammation. In particular we have shown that depletion of serotonin at the time of the development of the inflammatory episode reduces the severity of the inflammation. These findings suggest the possibility of novel therapeutic strategies targeting neurotransmitter systems to alleviate inflammation.
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PMID:The hypothalamic-pituitary-adrenal axis in autoimmunity. 929 47

It is now established that communication between the CNS and the immune system is bidirectional, that endocrine factors can alter immune function and that immune responses can alter both endocrine and CNS responses. In many respects CNS and endocrine responses to acute inflammation are similar to the changes associated with acute stress exposure. In contrast, during chronic inflammation associated with adjuvant induced arthritis (AA), although circulating levels of corticosterone are increased, the peptidergic regulation of the hypothalamus is different from that seen during acute stress. As the disease progresses, a paradoxical reduction occurs in CRH mRNA in the paraventricular nucleus (PVN), whereas PVN AVP mRNA increases. These data suggest that there is increased expression of AVP mRNA within the CRH cells of the PVN with an increased emphasis on AVP regulation of HPA output. Additionally, HPA function is altered during chronic inflammation such that responses to psychological stress (i.e. restraint) are significantly dampened, while responses to further inflammatory challenges are maintained. These data suggest that alterations in PVN peptide colocalization may be important in regulating the progression of peripheral inflammatory responses and that the effects of inflammation on the hypothalamus alter stress-responsive systems. In addition to the AA model, we have similarly observed alterations in PVN peptide mRNA expression with disease onset in the murine MRL lpr/lpr and MRL +/+ model of SLE. Disease onset in murine SLE is spontaneous and does not rely on exogenous application of adjuvant; however, decreased levels of CRH in the PVN were observed from early disease onset in this animal model. It is suggested that alterations in CRH regulation in response to either acute or chronic inflammation may contribute as etiological factors to both psychiatric (i.e. neuropsychiatric SLE) and stress-related disease.
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PMID:Inflammatory disease as chronic stress. 962 87

Low endogenous levels of dehydroepiandrosterone (DHEA) and/or its sulfoconjugated derivative DHEA-S have been associated with diseases such as lupus, cancer, and diabetes. Circulating concentrations of DHEA and DHEA-S resulting from endogenous production or hormone supplementation may also be relevant in psychiatric illness. Drugs may significantly increase or decrease circulating concentrations of these adrenal androgens by various mechanisms. Some agents, such as dexamethasone, affect the HPA axis by inhibiting ACTH and therefore decrease DHEA and DHEA-S concentrations. Central nervous system agents, including carbamazepine and phenytoin, induce the P450 enzymes that metabolize DHEA and DHEA-S and therefore decrease circulating concentrations of these hormones. Danazol alters the ratio between DHEA and DHEA-S by inhibiting sulfatase. As research moves forward to better understand the relationships of these adrenal androgens with health and disease, it is essential that studies be designed to control for the influence of administered pharmaceuticals on DHEA and DHEA-S.
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PMID:The influence of hormones and pharmaceutical agents on DHEA and DHEA-S concentrations: a review of clinical studies. 1186 61