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Query: UMLS:C0409974 (lupus)
 22,386 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Among the fatty acids, it is the omega-3 polyunsaturated fatty acids (PUFA) which possess the most potent immunomodulatory activities, and among the omega-3 PUFA, those from fish oil-eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)--are more biologically potent than alpha-linolenic acid (ALA). Some of the effects of omega-3 PUFA are brought about by modulation of the amount and types of eicosanoids made, and other effects are elicited by eicosanoid-independent mechanisms, including actions upon intracellular signaling pathways, transcription factor activity and gene expression. Animal experiments and clinical intervention studies indicate that omega-3 fatty acids have anti-inflammatory properties and, therefore, might be useful in the management of inflammatory and autoimmune diseases. Coronary heart disease, major depression, aging and cancer are characterized by an increased level of interleukin 1 (IL-1), a proinflammatory cytokine. Similarly, arthritis, Crohn's disease, ulcerative colitis and lupus erythematosis are autoimmune diseases characterized by a high level of IL-1 and the proinflammatory leukotriene LTB(4) produced by omega-6 fatty acids. There have been a number of clinical trials assessing the benefits of dietary supplementation with fish oils in several inflammatory and autoimmune diseases in humans, including rheumatoid arthritis, Crohn's disease, ulcerative colitis, psoriasis, lupus erythematosus, multiple sclerosis and migraine headaches. Many of the placebo-controlled trials of fish oil in chronic inflammatory diseases reveal significant benefit, including decreased disease activity and a lowered use of anti-inflammatory drugs.
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PMID:Omega-3 fatty acids in inflammation and autoimmune diseases. 1248 Jul 95

Heat shock proteins have been implicated as endogenous activators for dendritic cells (DCs). Without tissue distress or death, these intracellular molecules are inaccessible to surface receptor(s) on DCs, possibly to avoid uncontrolled DC activation and breakdown of immunologic tolerance. We herein addressed this hypothesis in transgenic mice by enforcing cell surface expression of gp96, a ubiquitous heat shock protein of the endoplasmic reticulum. Although a pan-specific promoter is used for transgene expression, neither the expression level nor the tissue distribution of the endogenous gp96 was altered by this maneuver. However, cell surface gp96 induced significant DC activations and spontaneous lupus-like autoimmune diseases, even though the development/functions of lymphocytic compartments were unaltered. Using a bone marrow chimera approach, we further demonstrated that both DC activation and autoimmunity elicited by cell surface gp96 are dependent on the downstream adaptor protein MyD88 for signaling by Toll/IL-1 receptor family. Our study not only established the proinflammatory property of cell surface gp96 in vivo, but also suggested a chronic stimulation of DCs by gp96 as a pathway to initiate spontaneous autoimmune diseases.
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PMID:Cell surface expression of an endoplasmic reticulum resident heat shock protein gp96 triggers MyD88-dependent systemic autoimmune diseases. 1466 29

Systemic lupus erythematosus (SLE) is an autoantibody and immune complex mediated disease. However, it is the ensuing inflammatory process that leads to irreversible organ damage. In fact several murine models of SLE suggest that this inflammatory organ damage can be prevented even in the presence of autoantibodies. Given data from experimental models as well as from patients, proinflammatory cytokines including tumour necrosis factor (TNF) alpha apparently play a significant role in the inflammatory process, but may have immunoregulatory functions at the same time. Therefore, anti-TNF alpha therapy may constitute an interesting candidate approach for treating SLE inflammatory organ disease, but potentially at the cost of increased autoantibody formation. Clinical trials will be required to answer whether TNF alpha blockade fulfils this hope with an acceptable safety profile. Interferon (IFN)-gamma, interleukin (IL)-18, IL-6 and possibly IL-1 are increased in SLE and likewise involved in the inflammatory process. Specific therapeutic agents for blocking these cytokines should be available in the near future.
Lupus 2004
PMID:Tumour necrosis factor and other proinflammatory cytokines in systemic lupus erythematosus: a rationale for therapeutic intervention. 1523 Feb 90

The treatment of rheumatoid arthritis (RA) has changed dramatically over the past 15 years with the realisation that earlier, aggressive therapy limits progression. There is evidence that biological response modifiers (BRMs), which target specific cytokines such as TNF-alpha and IL-1, are more effective than traditional disease-modifying antirheumatic drugs (DMARDs), especially in combination with methotrexate. Four therapies are approved for use in RA; three target TNF-alpha (etanercept [Enbrel, Amgen Inc.], infliximab [Remicade, Centocor Inc.], and adalimumab [Humira, Abbott]), and one targets IL-1 (anakinra [Kineret, Amgen Inc.]). It is clear from both the clinical trials and postmarketing reports that all four agents have a different safety profile compared with traditional DMARDs. There are several areas of concern with the use of the BRMs, which include serious and opportunistic infections, malignancy/lymphoma, congestive heart failure, demyelination, injection/infusion reactions, development of autoantibodies and lupus-like disease. It is important to be fully aware of the safety profile and differences between BRMs in order to use them appropriately.
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PMID:Considerations with the use of biological therapy in the treatment of rheumatoid arthritis. 1533 95

There is evidence from animal and human studies that IL-1 might play an important role in the development and maintainence of inflammation in systemic lupus erythemathosus (SLE). We hypothesized that, in SLE, there might be a relative deficiency in the physiologic antagonist of IL-1, IL-1 receptor antagonist (IL-1RA). We therefore treated three patients with active SLE in whom conventional therapy has failed with the human IL-1RA, Anakinra. In two of the three patients there was a transient effect on muscle pain and/or polyarthritis. In one patient with lupus myositis there was no effect at all. The therapy was well tolerated and the only significant side effect was a transient drop in complement levels (C3 and C4) without clinical or laboratory signs of increased SLE activity in all three patients.
Lupus 2004
PMID:IL-1RA in refractory systemic lupus erythematosus. 1546 91

Sex hormones seem to play an important role as modulators of the autoimmune disease onset/perpetuation. Generally, steroid hormones are implicated in the immune response, with estrogens as enhancers at least of the humoral immunity and androgens and progesterone (and glucocorticoids) as natural immunosuppressors. Synovial fluid levels (SF) of proinflammatory estrogens relative to androgens are significantly elevated in both male and female rheumatoid arthritis (RA) patients, as compared to controls, which is most probably due to increase of local enzymatic aromatase activity. Serum levels of estrogens have been found altered in RA patients, particularly estradiol in man. Thus, available steroid prehormones are rapidly converted to proinflammatory estrogens in the synovial tissue in the presence of inflammatory cytokines (i.e., TNFalpha, IL-1, IL-6). The increased estrogen concentrations observed in RA SF of both sexes are characterized mainly by the hydroxylated forms, in particular, 16alpha-hydroxyestrone, showing a mitogenic tumor growth stimulating role. Altered serum hydroxylated estrogens have been found also in serum of systemic lupus erythematosus (SLE) patients. As a matter of fact, our recent studies indicate that 17-beta estradiol (E2) clearly enhanced the expression of markers of cell growth and proliferation, whereas testosterone (T) induced an increase of markers indicating DNA damage and apoptosis. In particular, our data further shows that the enhancing role of estrogens on immune/inflammatory response is exerted by activating the NFkB complex pathway. In conclusion, locally increased estrogens (i.e., synovial tissue in RA or skin in SLE) might exert activating effects on cell proliferation, including macrophages and fibroblasts, suggesting new roles for estrogens in autoimmunity.
Lupus 2004
PMID:Sex hormones influence on the immune system: basic and clinical aspects in autoimmunity. 1548 92

Although far from complete, the picture of cytokines present in systemic lupus erythematosus (SLE) glomerulonephritis is already complex. Proinflammatory cytokines, such as TNF, IL-6, IL-1, and IL-18 are upregulated, as are both Th1 and Th2 cytokines, with different implications. In many instances, the local effects may be different from the systemic immunoregulatory ones. For some proinflammatory cytokines, and TNF in particular, the local proinflammatory ones may be more relevant to the disease. This may help solve discrepancies between different murine models of the disease and provide a better rationale for targeting certain cytokines in human SLE.
Lupus 2005
PMID:Cytokine expression in lupus kidneys. 1573 82

Atherosclerosis is recognized as the pathological basis of cardiovascular disease (CVD) and recent advances in basic science have shown that it should be considered as a chronic inflammatory process. Both elements of the innate and the adaptive immunity appear to be actively involved in atherogenesis. In fact, the potential role played by pattern-recognition receptors (Toll-like receptors and scavenger receptors), cytokines (such as IL-1, IL-6, TNFalpha), chemokines and pentraxines (such as CRP and PTX3) represents an emerging field of investigation in atherogenesis. In the near future we expect a better definition of the real biological and clinical impact on CVD of these mediators. On one side, they could become useful to complement traditional risk factors, in order to identify new categories of subjects prone to CVD development. On the other, they could become an additional potential target for therapeutic strategies.
Lupus 2005
PMID:Innate immunity and atherogenesis. 1621 80

Mycophenolate mofetil (MMF), a prodrug of mycophenolic acid (MPA), an inhibitor of inosine-5'-monophosphate dehydrogenase, has several immunosuppressant actions. MPA depletes guanosine and deoxyguanosine nucleotides preferentially in T and B lymphocytes, inhibiting proliferation and suppressing cell-mediated immune responses and antibody formation, major factors in acute and chronic rejection. MPA also can induce T-lymphocyte apoptosis. MPA suppresses dendritic cell maturation and can induce human monocyte-macrophage cell line differentiation, decreasing the expression of interleukin (IL)-1 and enhancing expression of the IL-1 receptor antagonist. In addition, MPA inhibits adhesion molecule glycosylation and expression and lymphocyte and monocyte recruitment. Activated macrophages produce nitric oxide (NO) and superoxide, which combine to generate tissue-damaging peroxynitrite. MPA depletes tetrahydrobiopterin and decreases NO production by inducible NO synthase without affecting constitutive NO synthase activity. By these mechanisms, MMF exerts anti-inflammatory activity, which could attenuate both acute and chronic rejection. Unlike calcineurin inhibitors, MMF is nonnephrotoxic and does not induce transforming growth factor-beta production, which is fibrogenic. MMF inhibits arterial smooth muscle cell proliferation, a contributor to graft proliferative arteriopathy, and does not increase blood pressure, cholesterol, or triglyceride levels. By decreasing high-density lipoprotein oxidation and macrophage recruitment, MMF also may delay onset/progression of graft atherosclerosis. Thus, MMF may prevent chronic rejection by several mechanisms. MMF activity is synergistic with that of other agents such as valganciclovir for treating cytomegalovirus infection. MMF also has synergistic activity with angiotensin-converting enzyme inhibitors or angiotensin II receptor antagonists in the treatment of some nephropathies in experimental animals. This combination may prevent progression toward end-stage renal disease in humans with chronic allograft, lupus, and diabetic nephropathies.
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PMID:Mechanisms of action of mycophenolate mofetil in preventing acute and chronic allograft rejection. 1625 60

This article collects the evidence that shows that the biological reactions to Silica are due to the stimulation of the Immune System. Both Innate and Adaptive Immunity are involved. The following sets of events take place sequentially: (1) Silica is recognized as a PAMP (pathogen-associated molecular pattern) by the Receptors of Innate Immunity; (2) This causes the stimulation first and then the death of the key cells of Innate Immunity (the macrophages); (3) While stimulated, macrophages produce cytokines (IL-1 and TNF) that stimulate fibroblasts; (4) The same and possibly other cytokines produced by silica- activated macrophages induce the maturation of dendritic cells, which are the connecting elements between the Innate and the Adaptive (lymphoid) Immune Systems; (5) It follows a polyclonal activation of the Adaptive Immunity; (6) The end result is the formation of fibro-hyaline tissue. In view of the double involvement of the Innate and the Adaptive Immune Systems and their cooperation in the stimulation of fibrosis, Silicosis can be considered as a "Collagen" Disease, related to other diseases of that group like Rheumatoid Arthritis, Lupus erythematosus and Scleroderma. Not surprisingly the incidence of these Diseases has been shown to be significantly increased in human exposed to Silica.
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PMID:Silica and the immune system. 1635 May 48


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