Lupus and the Seed

Dr. Weeks’ Comment: SLE – lupus is an inflammatory disease and sadly almost  all the anti-inflammatory agents on the market have toxic side-effects.  Steroids (immune-suppressive) NSAIDs (toxic to kidney and liver function) but if you eat the seeds your body can heal.

 

“…Systemic lupus erythematosus (SLE) is an autoimmune disease that involves multiple organs and is characterized by persistent systemic inflammation…”

 

“…Systemic lupus erythematous (SLE) is an autoimmune disorder that primarily affects young women and is characterized by inflammation in several organs including the kidneys, skin, joints, blood, and nervous system…”

 

 

ARTICLES IN THE PEER-REVIEWED SCIENTIFIC LITERATURE

 

J Intern Med. 2015 Feb 26. doi: 10.1111/joim.12357. [Epub ahead of print]

Pathogenic immunity in systemic lupus erythematous and atherosclerosis: common mechanisms and possible targets for intervention.

Wigren M1, Nilsson J, Kaplan MJ.

 

 

Abstract

Systemic lupus erythematous (SLE) is an autoimmune disorder that primarily affects young women and is characterized by inflammation in several organs including the kidneys, skin, joints, blood, and nervous system. Abnormal immune cellular and humoral responses play important roles in the development of the disease process. Impaired clearance of apoptotic material is a key factor contributing to activation of self-reactive immune cells. The incidence of atherosclerotic cardiovascular disease (CVD) is increased up to 50-fold in SLE patients compared to age- and gender-matched control subjects and this can only partly be explained by traditional risk factors for CVD……

 

Handb Exp Pharmacol. 2015;224:455-82. doi: 10.1007/978-3-319-09665-0_14.

Impact of systemic inflammation and autoimmune diseases on apoA-I and HDL plasma levels and functions.

Montecucco F1,

 

The cholesterol of high-density lipoproteins (HDLs) and its major proteic component, apoA-I, have been widely investigated as potential predictors of acute cardiovascular (CV) events. In particular, HDL cholesterol levels were shown to be inversely and independently associated with the risk of acute CV diseases in different patient populations, including autoimmune and chronic inflammatory disorders. Some relevant and direct anti-inflammatory activities of HDL have been also recently identified targeting both immune and vascular cell subsets. These studies recently highlighted the improvement of HDL function (instead of circulating levels) as a promising treatment strategy to reduce inflammation and associated CV risk in several diseases, such as systemic lupus erythematosus and rheumatoid arthritis. In these diseases, anti-inflammatory treatments targeting HDL function might improve both disease activity and CV risk.

 

 

Eur Heart J. 2015 Feb 21;36(8):482-489. Epub 2014 Nov 27.

Cardiovascular disease in patients with chronic inflammation: mechanisms underlying premature cardiovascular events in rheumatologic conditions.

Mason JC1, Libby P2.

 

 

Abstract

A variety of systemic inflammatory rheumatic diseases associate with an increased risk of atherosclerotic events and premature cardiovascular (CV) disease. Although this recognition has stimulated intense basic science and clinical research, the precise nature of the relationship between local and systemic inflammation, their interactions with traditional CV risk factors, and their role in accelerating atherogenesis remains unresolved. The individual rheumatic diseases have both shared and unique attributes that might impact CV events. Understanding of the positive and negative influences of individual anti-inflammatory therapies remains rudimentary.

Lupus. 2014 Nov 21. pii: 0961203314559085. [Epub ahead of print]

Matrix metalloproteinase 9 polymorphisms and systemic lupus erythematosus: correlation with systemic inflammatory markers and oxidative stress.

Bahrehmand F1, Vaisi-Raygani A2, Kiani A3, Rahimi Z4, Tavilani H5, Ardalan M6, Vaisi-Raygani H7, Shakiba E8, Pourmotabbed T9.

 

Systemic lupus erythematosus (SLE) is an autoimmune disease that involves multiple organs and is characterized by persistent systemic inflammation. Among the effects of inflammatory mediators, the induction of matrix metalloproteinases-2 and -9 (MMP-2 and MMP-9) and oxidative stress has been demonstrated to be important in the development of SLE. In this study, the possible association between MMP-9 and MMP-2 functional promoter polymorphism, stress, and inflammatory markers with development of severe cardiovascular disease (CVD), high blood pressure (HBP), and lupus nephropathy (LN) in SLE patients was investigated. ….This study for the first time not only suggests that MMP-9 -C1562 T and MMP-2 -G1575A alleles synergistically increase the risk of SLE but also high serum levels of MDA, neopterin, and circulatory levels of MMP-2 and lower MMP-9 in SLE patients. This information may be important in the evaluation of SLE progression and in the elucidation of the mechanisms of the disease pathogenesis.

 

Nephron Clin Pract. 2014;128(3-4):224-31. doi: 10.1159/000368581. Epub 2014 Nov 8.

Lupus nephritis: from pathogenesis to targets for biologic treatment.

Liu Y1, Anders HJ.

 

Abstract

BACKGROUND/AIMS:

Lupus nephritis is an organ manifestation of systemic autoimmunity. Current treatment algorithms are still based on unselective immunosuppressive drugs. There is hope that highly selective biological drugs could be as or even more effective but less toxic. A profound understanding of the pathogenesis of lupus nephritis is necessary to identify the optimal molecular targets.

RESULTS:

The pathogenesis of lupus nephritis is based (1) on the mechanisms that lead to loss of tolerance against nuclear autoantigens, i.e. systemic lupus, and then (2) on the mechanisms of immune complex-induced intrarenal inflammation. … Activation of B cells and their maturation to plasma cells promotes autoantibody production and subsequent immune complex glomerulonephritis. Complement and numerous proinflammatory cytokines drive the inflammatory process that can cause kidney injury, scarring, and chronic kidney disease.

CONCLUSION:

Systemic lupus is more a variable syndrome than a single disorder based on heterogeneous genetic variants and complex aberrant immune alterations. This makes it less likely that a single specific biological drug will be as efficient as currently used unselective immunosuppressive drugs. Autoantibody production and intrarenal immune complex formation are the hallmark of lupus nephritis. However, kidney injury and scarring also result from local amplification of tissue inflammation. Therefore, a combination of unselective immunosuppressive and biological drugs that block immune cell recruitment of proinflammatory cytokines may be promising to improve disease outcomes in lupus nephritis.

 

 

 

Nephrol Dial Transplant. 2014 Sep 23. pii: gfu302. [Epub ahead of print]

CD147 (EMMPRIN/Basigin) in kidney diseases: from an inflammation and immune system viewpoint.

Kosugi T1, Maeda K1, Sato W1, Maruyama S1, Kadomatsu K2.

 

The glycosylated transmembrane protein CD147/basigin, also known as extracellular matrix metalloproteinase (MMP) inducer (EMMPRIN), contributes to cell survival, migration and cancer invasion. In normal kidneys, high expression of CD147 is detected only in the basolateral side of tubular epithelial cells (TECs). The pathophysiological roles of CD147 in the kidneys are diverse, ranging from involvement in the occurrence of acute kidney injury (AKI) that is frequently accompanied by ischemia, inflammation and a loss of self-tolerance to the progression of chronic kidney disease (CKD) that is caused by an imbalance in extracellular matrix protein turnover. In AKI induced by ischemia, it is the CD147 on neutrophils, rather than that on TECs, that coordinately participates in massive neutrophil recruitment via acting as a physiological ligand for E-selectin, which is specifically enhanced in the endothelium upon inflammatory stimulation. …… Disruption of such a vicious chain reaction involving CD147 would therefore be required in order to overcome kidney diseases. Multidisciplinary research regarding CD147 functions may open a new avenue for targeting therapeutics for kidney diseases.

 

 

Egypt J Immunol. 2014;21(1):1-12.

Interleukin-18 gene polymorphisms in systemic lupus erythematosus: relation to disease status.

Fouad NA, Baraka EA, Hassan WA.

Abstract

Systemic lupus erythematosus (SLE) is a multisystem autoimmune connective tissue disorder characterized by loss of self-tolerance causing immune-mediated tissue destruction and various clinical presentations Interleukin-18 (IL-18) is a proinflammatory cytokine that plays an important role in chronic inflammation and autoimmune disorders. This study investigates polymorphisms of the IL-18 gene in SLE patients at positions -607 and -137 of the promoter to elucidate their possible roles in the activity and severity of this disease. Fifty SLE patients and fifty unrelated healthy control group were included. AII SLE patients underwent thorough clinical examination and SLE disease activity assessment using SLEDAI…… Significantly elevated levels of plasma IL-18 were found in patients compared to controls (P < 0.001) and those with genotype CC at -607 demonstrated the highest IL-18 level (331.74 +/- 36.48 pg/mL). Serum IL-18 levels showed significant positive correlations with the ESR 1st hr. (r = 0.89), protein/creatinine ratios (r = 0.88), anti-dsDNA titers (r = 0.44) and SLEDAI scores (r = 0.91). In contrast, significant negative correlations were found with HB% r = -0.68, creatinine clearance (r = -0.87) and C3 (r = -0.81). In addition, a statistically significant association was found between IL-18 of CC -607 genotype and lupus nephritis, arthritis and immunological disorders. In conclusion, IL-18 promoter gene polymorphisms at position -607 may contribute to SLE activity and accelerate SLE development by enhancing production of IL-18 protein in SLE patients.

 

 

 

Clin Exp Rheumatol. 2014 Sep-Oct;32(5):705-14. Epub 2014 Aug 15.

Blockade of macrophage autophagy ameliorates activated lymphocytes-derived DNA induced murine lupus possibly via inhibition of proinflammatory cytokine production.

Li B1, Yue Y, Dong C, Shi Y, Xiong S.

 

Systemic lupus erythematosus (SLE) is a typical inflammatory autoimmune disease for its unknown pathogenesis and potential fatality. It has been reported that autophagy has a crosstalk with autoimmunity, but its impact on the pathogenesis of SLE remains unclear. Here, we investigated the role of autophagy in inflammatory response of macrophages under SLE conditions.

RESULTS:

We found that autophagy related genes were significantly upregulated in the splenic and renal macrophages of lupus mice and in the PBMC of SLE patients. Adoptive transfer of Beclin 1 knockdown macrophages could significantly decrease the anti-dsDNA antibodies and proteinuria levels, robustly reduce renal immune complex deposition and remit glomerulonephritis, indicating the amelioration of murine lupus. This protective effect was associated with the obviously decreased production of proinflammatory cytokines IL-6 and TNF-α.

CONCLUSIONS:

Our results suggested that aberrant activated autophagy in macrophages contributed to the pathogenesis of murine lupus possibly via promoting the production of proinflammatory cytokines TNF-α and IL-6, and inhibition of autophagy might represent a novel regulation strategy for excessive activation of proinflammatory macrophages and a new therapeutic regime for SLE.

 

 

Autoimmun Rev. 2014 Dec;13(12):1174-81. doi: 10.1016/j.autrev.2014.08.019. Epub 2014 Aug 23.

Th17 cells in inflammation and autoimmunity.

Singh RP1, Hasan S2, Sharma S3, Nagra S4, Yamaguchi DT3, Wong DT5, Hahn BH4, Hossain A4.

 

Lupus. 2014 Dec;23(14):1460-7. doi: 10.1177/0961203314543915. Epub 2014 Jul 23.

Elevated C-reactive protein and self-reported disease activity in systemic lupus erythematosus.

Eudy AM1, Vines AI2, Dooley MA3, Cooper GS4, Parks CG5.

 

C-reactive protein (CRP), a biomarker of inflammation, has been associated with increased disease activity in rheumatoid arthritis. However, the association in systemic lupus erythematosus (SLE) remains unclear. We examined the association of CRP with self-reported disease activity in the Carolina Lupus Study and described differences by sociodemographic characteristics. The study included baseline and three-year follow-up data on 107 African-American and 69 Caucasian SLE patients enrolled at a median 13 months since diagnosis. ….These findings suggest that CRP may be a useful marker in studies of SLE

 

 

 

Arthritis Rheumatol. 2014 Sep;66(9):2521-31. doi: 10.1002/art.38716.

Interleukin-6 deficiency corrects nephritis, lymphocyte abnormalities, and secondary Sjögren’s syndrome features in lupus-prone Sle1.Yaa mice.

Maier-Moore JS1, Horton CG, Mathews SA, Confer AW, Lawrence C, Pan Z, Coggeshall KM, Farris AD.

RESULTS:

IL-6 deficiency not only ameliorated autoantibody production and renal disease in this model, but also effectively reduced inflammation of lungs and salivary glands. Furthermore, IL-6 deficiency abrogated differentiation of Th1 and extrafollicular T helper cells, germinal center B cells, and plasma cells in the spleen and eliminated renal T cells with IL-17, interferon-γ, and IL-21 production potential.

CONCLUSION:

Our findings highlight IL-6-mediated T cell aberrations in Yaa-driven autoimmunity and support the concept of therapeutic IL-6/IL-6 receptor blockade in systemic lupus erythematosus and Sjögren’s syndrome by impairing the production of autoantibodies and lymphocytic infiltration of the kidneys, lungs, and salivary glands.

 

 

 

GRAPE SEED EXTRACT – very BENEFICIAL

 

PLoS One. 2014 Dec 11;9(12):e114792. doi: 10.1371/journal.pone.0114792. eCollection 2014.

Resveratrol possesses protective effects in a pristane-induced lupus mouse model.

Wang ZL1, Luo XF1, Li MT1, Xu D1, Zhou S1, Chen HZ2, Gao N1, Chen Z1, Zhang LL1, Zeng XF1.

BACKGROUND:

Systemic lupus erythematosus (SLE) is a multisystemic autoimmune disease characterized by the production of autoantibodies. To date, no therapy has been found to satisfactorily treat SLE. SIRT1 deficiency results in the development of an autoimmune syndrome in mice, including a high titer of anti-nuclear antibody in serum, immunoglobulin deposition in the kidney, and immune complex glomerulonephritis. Resveratrol is an activator of SIRT1 and possesses anti-inflammation and immune-regulatory properties.

RESULTS:

Resveratrol attenuated proteinuria, immunoglobuin depositon in kidney, and glomerulonephritis as well as IgG1 and IgG2a in serum in pristane-induced lupus mice. Resveratrol also suppressed CD69 and CD71 expression on CD4+ T cells as well as CD4+ T cell proliferation, induced CD4+ T cell apoptosis, and decreased CD4 IFNγ+ Th1 cells and the ratio of Th1/Th2 cells in vitro. In vitro antibody production and proliferation of B cells were also inhibited.

CONCLUSION: Resveratrol possesses protective effects in pristane-induced lupus mice and may represent a novel approach for the management of SLE.

 

 

 

VITAMIN D 3 HELPS

 

J Bras Nefrol. 2014 Oct-Dec;36(4):430-6. doi: 10.5935/0101-2800.20140062.

Association of hypovitaminosis D with Systemic Lupus Erythematosus and inflammation.

de Souza VA1,

 

Nowadays it is described a high prevalence of hypovitaminosis D in Systemic Lupus Erythematosus (SLE), which is associated with some clinical manifestations and increased inflammatory activity.

RESULTS:

The prevalence of 25(OH)D insufficiency was 55% in SLE patients and 8% in the controls participants (p = 0.001). The median of 25(OH)D was lower in patients than in controls. Patients with insufficient 25(OH)D had higher levels of IL-6 and higher prevalence of hematuria in the AES. There was no correlation between vitamin D and SLEDAI or lupus nephritis.

CONCLUSION:

In our study, vitamin D deficiency was more prevalent in patients with SLE and was associated with higher levels of IL-6 and hematuria.

 

 

 

WALKING HELPS

J Appl Physiol (1985). 2014 Sep 15;117(6):639-47. doi: 10.1152/japplphysiol.00486.2014. Epub 2014 Jul 18.

Exercise training can attenuate the inflammatory milieu in women with systemic lupus erythematosus.

Perandini LA1, Sales-de-Oliveira D1, Mello SB1, Camara NO2, Benatti FB3, Lima FR1, Borba E1, Bonfa E1, Sá-Pinto AL1, Roschel H3, Gualano B4.

 

 

Abstract

Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by chronic inflammation. This study sought to assess the effects of an exercise training program on cytokines and soluble TNF receptors (sTNFRs) in response to acute exercise in SLE women. Eight SLE women and 10 sex-, age-, and body mass index-comparable healthy controls (HC) participated in this study. Before and after a 12-wk aerobic exercise training program, cytokines and sTNFRs were assessed at rest and in response to single bouts of acute moderate/intense exercise. HC performed the acute exercise bouts only at baseline. After the exercise training program, there was a decrease in resting TNFR2 levels (P = 0.025) and a tend to reduction interleukin (IL)-10 levels (P = 0.093) in SLE. The resting levels of IL-6, IL-10, and TNF-α after the exercise training in SLE reached HC levels (P > 0.05). In response to a single bout of acute moderate exercise, the area under the curve (AUC) of IL-10 was significantly reduced after the exercise training program in SLE (P = 0.043), and the AUC of IL-10, IL-6, TNF-α, and sTNFR1 of SLE approached control values (P > 0.05). In response to a single bout of acute intense exercise, the AUC of IL-10 was significantly reduced in SLE (P = 0.015). Furthermore, the AUC of sTNFR2 tended to decrease after exercise training program in SLE (P = 0.084), but it did not reach control values (P = 0.001). An aerobic exercise training program attenuated the inflammatory milieu in SLE women, revealing a novel homeostatic immunomodulatory role of exercise in an autoimmunity condition.

 

 

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