Dietary Supplementation With Eicosapentaenoic Acid Inhibits Plasma Cell Differentiation and Attenuates Lupus Autoimmunity.

Accumulating evidence suggests that cholesterol accumulation in leukocytes is causally associated with the development of autoimmune diseases. However, the mechanism by which fatty acid composition influences autoimmune responses remains unclear. To determine whether the fatty acid composition of diet modulates leukocyte function and the development of systemic lupus erythematosus, we examined the effect of eicosapentaenoic acid (EPA) on the pathology of lupus in drug-induced and spontaneous mouse models. We found that dietary EPA supplementation ameliorated representative lupus manifestations, including autoantibody production and immunocomplex deposition in the kidneys. A combination of lipidomic and membrane dynamics analyses revealed that EPA remodels the lipid composition and fluidity of B cell membranes, thereby preventing B cell differentiation into autoantibody-producing plasma cells. These results highlight a previously unrecognized mechanism by which fatty acid composition affects B cell differentiation into autoantibody-producing plasma cells during autoimmunity, and imply that EPA supplementation may be beneficial for therapy of lupus.

Lupus, Silica, and Dietary Omega-3 Fatty Acid Interventions.

Two environmental factors, crystalline silica (cSiO2), a toxic airborne particle encountered occupationally, and docosahexaenoic acid (DHA), a dietary omega-3 highly unsaturated fatty acid (HUFA), have the potential to influence the development of systemic lupus erythematosus (lupus). Using the NZBWF1 mouse, which spontaneously develops lupus, we found that intranasal exposure to cSiO2 significantly decreases latency and promotes rapid progression of the disease. Specifically, cSiO2 induces the development of ectopic lymphoid structures (ELS) containing germinal centers in the lungs that yield vigorous and diverse autoantibody responses locally and systemically. Transcriptomic analysis revealed that cSiO2 promotes a robust type I interferon gene signature that likely precipitates ELS neogenesis. Intriguingly, dietary supplementation with human-relevant doses of DHA impedes cSiO2-induced gene expression, ELS neogenesis, autoantibody elevation, and glomerulonephritis in this lupus-prone mouse model. Together, our findings point to the feasibility of enhancing tissue omega-3 HUFAs as a personalized nutritional intervention to impede onset and progression of environment-triggered autoimmune disease.

Dietary Docosahexaenoic Acid Prevents Silica-Induced Development of Pulmonary Ectopic Germinal Centers and Glomerulonephritis in the Lupus-Prone NZBWF1 Mouse.

Ectopic lymphoid structures (ELS) consist of B-cell and T-cell aggregates that are initiated de novo in inflamed tissues outside of secondary lymphoid organs. When organized within follicular dendritic cell (FDC) networks, ELS contain functional germinal centers that can yield autoantibody-secreting plasma cells and promote autoimmune disease. Intranasal instillation of lupus-prone mice with crystalline silica (cSiO2), a respirable particle linked to human lupus, triggers ELS formation in the lung, systemic autoantibodies, and early onset of glomerulonephritis. Here we tested the hypothesis that consumption of docosahexaenoic acid (DHA), an ω-3 polyunsaturated fatty acid with anti-inflammatory properties, influences the temporal profile of cSiO2-induced pulmonary ectopic germinal center formation and development of glomerulonephritis. Female NZBWF1 mice (6-wk old) were fed purified isocaloric diets supplemented with 0, 4, or 10 g/kg DHA - calorically equivalent to 0, 2, or 5 g DHA per day consumption by humans, respectively. Beginning at age 8 wk, mice were intranasally instilled with 1 mg cSiO2, or saline vehicle alone, once per wk, for 4 wk. Cohorts were sacrificed 1, 5, 9, or 13 wk post-instillation (PI) of the last cSiO2 dose, and lung and kidney lesions were investigated by histopathology. Tissue fatty acid analyses confirmed uniform dose-dependent DHA incorporation across all cohorts. As early as 1 wk PI, inflammation comprising of B (CD45R+) and T (CD3+) cell accumulation was observed in lungs of cSiO2-treated mice compared to vehicle controls; these responses intensified over time. Marked follicular dendritic cell (FDC; CD21+/CD35+) networking appeared at 9 and 13 wk PI. IgG+ plasma cells suggestive of mature germinal centers were evident at 13 wk. DHA supplementation dramatically suppressed cSiO2-triggered B-cell, T-cell, FDC, and IgG+ plasma cell appearance in the lungs as well as anti-dsDNA IgG in bronchial lavage fluid and plasma over the course of the experiment. cSiO2 induced glomerulonephritis with concomitant B-cell accumulation in the renal cortex at 13 wk PI but this response was abrogated by DHA feeding. Taken together, realistic dietary DHA supplementation prevented initiation and/or progression of ectopic lymphoid neogenesis, germinal center development, systemic autoantibody elevation, and resultant glomerulonephritis in this unique preclinical model of environment-triggered lupus.

Conjugated linoleic acid prevents age-dependent neurodegeneration in a mouse model of neuropsychiatric lupus via the activation of an adaptive response.

Oxidative stress is a key mediator of autoimmune/neurodegenerative disorders. The antioxidant/anti-inflammatory effect of a synthetic conjugated linoleic acid (CLA) mixture in MRL/MpJ-Fas lpr mice (MRL/lpr), an animal model of neuropsychiatric lupus, was previously associated with the improvement of nuclear factor-E2-related factor 2 (Nrf2) defenses in the spleen and liver. However, little is known about the neuroprotective ability of a CLA mixture. This study investigated the age-dependent progression of oxidative stress and the hyperactivation of redox-sensitive compensatory pathways (macroautophagy, Nrf2) in old/diseased MRL/lpr mice brains and examines the effect produced by dietary CLA supplementation. Disrupted redox homeostasis was evidenced in the blood, liver, and brain of 21- to 22-week-old MRL/lpr (Old) mice compared with 8- to 10-week-old MRL/lpr (Young) animals. This alteration was associated with significant hyperactivation of compensatory mechanisms (macroautophagy, Nrf2, and astrocyte activation) in the brains of Old mice. Five-week daily supplementation with CLA (650 mg/kg-1 body weight) of 16-week-old (CLA+Old) mice diminished all the pathological hallmarks at a level comparable to Young mice or healthy controls (BALB/c). Such data demonstrated that MRL/lpr mice can serve as a valuable model for the evaluation of the effectiveness of neuroprotective drugs. Notably, the preventive effect provided by CLA supplementation against age-associated neuronal damage and hyperactivation of compensatory mechanisms suggests that the activation of an adaptive response is at least in part accountable for its neuroprotective ability.

Vitamin D supplementation in the prevention and management of major chronic diseases not related to mineral homeostasis in adults: research for evidence and a scientific statement from the European society for clinical and economic aspects of osteoporosis and osteoarthritis (ESCEO).

INTRODUCTION: Optimal vitamin D status promotes skeletal health and is recommended with specific treatment in individuals at high risk for fragility fractures. A growing body of literature has provided indirect and some direct evidence for possible extraskeletal vitamin D-related effects. PURPOSE AND METHODS: Members of the European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis have reviewed the main evidence for possible proven benefits of vitamin D supplementation in adults at risk of or with overt chronic extra-skeletal diseases, providing recommendations and guidelines for future studies in this field. RESULTS AND CONCLUSIONS: Robust mechanistic evidence is available from in vitro studies and in vivo animal studies, usually employing cholecalciferol, calcidiol or calcitriol in pharmacologic rather than physiologic doses. Although many cross-sectional and prospective association studies in humans have shown that low 25-hydroxyvitamin D levels (i.e., <50 nmol/L) are consistently associated with chronic diseases, further strengthened by a dose-response relationship, several meta-analyses of clinical trials have shown contradictory results. Overall, large randomized controlled trials with sufficient doses of vitamin D are missing, and available small to moderate-size trials often included people with baseline levels of serum 25-hydroxyvitamin D levels >50 nmol/L, did not simultaneously assess multiple outcomes, and did not report overall safety (e.g., falls). Thus, no recommendations can be made to date for the use of vitamin D supplementation in general, parental compounds, or non-hypercalcemic vitamin D analogs in the prevention and treatment of extra-skeletal chronic diseases. Moreover, attainment of serum 25-hydroxyvitamin D levels well above the threshold desired for bone health cannot be recommended based on current evidence, since safety has yet to be confirmed. Finally, the promising findings from mechanistic studies, large cohort studies, and small clinical trials obtained for autoimmune diseases (including type 1 diabetes, multiple sclerosis, and systemic lupus erythematosus), cardiovascular disorders, and overall reduction in mortality require further confirmation.

Assessment of 1,25-dihydroxyvitamin D3 effects on Treg cells in a mouse model of systemic lupus erythematosus.

CONTEXT: Systemic lupus erythematosus (SLE) is a chronic autoimmune disease which is characterized by the presence of auto-reactive T cell and anti-ds DNA antibodies. Treg cells are crucial for maintaining immunologic self-tolerance and are shown to be reduced in SLE patients. 1,25-Dihydroxyvitamin D3 has immunomedulatory effects on the immune system and has recently received substantial attention. OBJECTIVE: In this study we evaluated the effects of 1,25-dihydroxyvitamin D3 on Treg cells and related cytokines in lupus-like induced mice model. MATERIALS AND METHODS: Female Balb/c mice were divided into four groups: Group one: injected with PBS and Freund's adjuvant; Group two: injected with non-activated chromatin; Group three: Lupus-like disease was induced with activated chromatin; Group four: Mice were initially treated for two weeks with 1,25-dihydroxyvitamin D3 and then lupus-like disease was induced. Group five: Four mice from group one were treated with 1,25-dihydroxyvitamin D3 for two weeks after disease establishment. Ten weeks after the last injection the mice were killed and spleens were studied for Treg percentages and expression of cytokine genes. RESULTS: We found that treatment with 1,25-dihydroxyvitamin D3 reduces IL-6 and IL-10 mRNA expression and increases TGF-ß and Foxp3 mRNA expression levels, and also enhances spleen Treg percentage. CONCLUSIONS: The remarkable reduction of IL-6 and IL-10 gene expressions, significant enhancement of TGF-ß and Foxp3 gene expressions, along with an increase in Treg cell population after oral 1,25-dihydroxyvitamin D3 administration suggest a possible role for this vitamin as a prophylactic supplement in SLE.

Nuevas dianas terapéuticas en el lupus sistémico (parte 2/2) / New targets in systemic lupus (part 2/2)

Glucocorticoides, aspirina, antipalúdicos e inmunosupresores convencionales constituyen la base del tratamiento del lupus eritematoso sistémico (LES). Hasta recientemente, los 3 primeros eran los únicos agentes aprobados para su tratamiento. El mejor conocimiento de la fisiopatología del sistema inmunitario ha permitido identificar nuevas dianas terapéuticas. De hecho, belimumab, un anticuerpo monoclonal humano inhibidor de BLyS, se ha convertido hace pocos meses en el primer fármaco aprobado para el tratamiento del LES desde 1957, lo que subraya las dificultades de todo tipo, incluyendo las económicas y organizativas, inherentes a los ensayos clínicos sobre esta enfermedad. Otras muchas moléculas se encuentran en distintas fases de desarrollo y en poco tiempo dispondremos de resultados concretos. En esta revisión repasamos el mecanismo de acción y los datos clínicos más relevantes de estas moléculas (AU)

Glucocorticoids, aspirin, conventional antimalarials and immunosuppressants are the mainstay of treatment of Systemic Lupus Erythematosus (SLE). Until recently, the first three were the only agents approved for treatment. A better understanding of the pathophysiology of the immune system has identified new therapeutic targets. In fact, belimumab, a human monoclonal antibody to BLyS inhibitor has become, in recent months, the first drug approved for the treatment of SLE since 1957, underscoring difficulties of all kinds, including economic and organizational ones inherent to clinical trials on this disease. Many other molecules are in various stages of development and soon will have concrete results. In this review, we examined the mechanism of action and most relevant clinical data for these molecules (AU)

Dietary intake of vitamin D during adolescence and risk of adult-onset systemic lupus erythematosus and rheumatoid arthritis.

OBJECTIVE: Vitamin D has immunomodulatory properties with potential etiologic implications for autoimmune diseases. The relevant exposure time during which vitamin D may influence disease risk is unknown. Our objective was to examine the relationship between reported vitamin D intake during adolescence and adult-onset rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) incidence in prospective cohort studies of women, the Nurses' Health Study (NHS) and the Nurses' Health Study II (NHSII). METHODS: Food frequency questionnaires concerning high school diet completed by 73,629 NHS (1986) and 45,544 NHSII (1998) participants were used to calculate nutrient intakes during adolescence. Incident RA and SLE cases prior to 2006 (NHS) and 2007 (NHSII) were confirmed by medical record review. Cox proportional hazards models calculated relative risks and 95% confidence intervals of incident RA and SLE according to quintile cutoffs of vitamin D intake. Age- and calorie-adjusted and multivariable-adjusted (including sun exposure factors) analyses were completed. Random-effects models were used to meta-analyze estimates of association from the 2 cohorts. RESULTS: Incident RA was confirmed in 652 NHS and 148 NHSII participants and SLE was confirmed in 122 NHS and 54 NHSII participants over a mean followup time of 351 months (NHS) and 209 months (NHSII). Age- and calorie-adjusted and multivariable-adjusted models did not show significant associations between adolescent vitamin D intake and risk of adult-onset RA or SLE. CONCLUSION: We did not find associations between adolescent dietary vitamin D intake and adult RA or SLE risk among NHS and NHSII women, suggesting that other time periods during the life course should be studied.

Antioxidant intake and risks of rheumatoid arthritis and systemic lupus erythematosus in women.

Antioxidants may protect against development of rheumatoid arthritis or systemic lupus erythematosus by combating oxidative stress. The authors identified and confirmed incident cases of rheumatoid arthritis and systemic lupus erythematosus among 184,643 US women followed in the Nurses' Health Study and Nurses' Health Study II cohorts in 1980-2004. Semiquantitative food frequency questionnaires assessed intakes of vitamins A, C, and E and alpha-carotene, beta-carotene, beta-cryptoxanthin, lycopene, lutein, and zeaxanthin from foods and supplements. The authors examined total antioxidant intake by calculating a "ferric-reducing ability of plasma" score, a new method for quantifying the total antioxidant effect of a food based on the reduction of ferric to ferrous iron by antioxidants. Cumulative updated total energy-adjusted dietary intakes were used. Associations between intake of each nutrient and incident rheumatoid arthritis and systemic lupus erythematosus were examined in age-adjusted and Cox proportional hazards models, adjusted for confounders. Results from the cohorts were pooled meta-analytically by using random-effects models. The authors identified 787 incident rheumatoid arthritis cases and 192 systemic lupus erythematosus cases for whom prospective dietary information was available. In these large, prospective cohorts of women, antioxidant intake was not associated with the risk of developing either rheumatoid arthritis or systemic lupus erythematosus.

Immunological alterations in lupus-prone autoimmune (NZB/NZW) F1 mice by mycelia Chinese medicinal fungus Cordyceps sinensis-induced redistributions of peripheral mononuclear T lymphocytes.

Mycelia products from wild-form Cordyceps sinensis could be constantly produced in a large scale and would be a better source of this herbal medicine. Our purpose was to investigate the immunological effects of an orally administered hot-water extract cultured mycelium of C. sinensis in lupus-prone (NZB/NZW) F1 hybrids. Forty female mice were divided into four groups and were given 2.4 mg/g/day oral doses of C. sinensis starting at three (group A), six (group B), or eight (group C) months of age, whereas the remaining group (group D) served as a control. Survival, proteinuria, and titers of anti-double-stranded DNA autoantibodies were evaluated. Treatment with C. sinensis resulted in increased survival, decreased proteinuria, and reduced titers of anti-double-stranded DNA antibody in groups A and B. Moreover, the mice in groups A and B showed significantly reduced percentages of CD4(+) T cells (*P < 0.05) and increased percentages of CD8(+) T cells in peripheral blood mononuclear cells (PBMC) after C. sinensis administration. At 6 months of age, the proliferation rate of BrdU-incorporated spleen cells was significantly decreased after 48 and 72 h of C. sinensis treatment (**P < 0.01) in group A of mice. In conclusions, early medication with C. sinensis induced the redistribution of PBMC and attenuated the disease severity of lupus in (NZB/NZW) F1 mice.

Vaccination-induced systemic autoimmunity in farmed Atlantic salmon.

Over half of the salmon consumed globally are farm-raised. The introduction of oil-adjuvanted vaccines into salmon aquaculture made large-scale production feasible by preventing infections. The vaccines that are given i.p. contain oil adjuvant such as mineral oil. However, in rodents, a single i.p. injection of adjuvant hydrocarbon oil induces lupus-like systemic autoimmune syndrome, characterized by autoantibodies, immune complex glomerulonephritis, and arthritis. In the present study, whether the farmed salmon that received oil-adjuvanted vaccine have autoimmune syndrome similar to adjuvant oil-injected rodents was examined. Sera and tissues were collected from vaccinated or unvaccinated Atlantic salmon (experimental, seven farms) and wild salmon. Autoantibodies (immunofluorescence, ELISA, and immunoprecipitation) and IgM levels (ELISA) in sera were measured. Kidneys and livers were examined for pathology. Autoantibodies were common in vaccinated fish vs unvaccinated controls and they reacted with salmon cells/Ags in addition to their reactivity with mammalian Ags. Diffuse nuclear/cytoplasmic staining was common in immunofluorescence but some had more specific patterns. Serum total IgM levels were also increased in vaccinated fish; however, the fold increase of autoantibodies was much more than that of total IgM. Sera from vaccinated fish immunoprecipitated ferritin and approximately 50% also reacted with other unique proteins. Thrombosis and granulomatous inflammation in liver, and immune-complex glomerulonephritis were common in vaccinated fish. Autoimmunity similar to the mouse model of adjuvant oil-induced lupus is common in vaccinated farmed Atlantic salmon. This may have a significant impact on production loss, disease of previously unknown etiology, and future strategies of vaccines and salmon farming.

Vitamin D intake and risks of systemic lupus erythematosus and rheumatoid arthritis in women.

OBJECTIVES: Vitamin D has immune-modulating effects and may protect against the development of systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). METHODS: We identified incident cases of SLE and RA among 186 389 women followed from 1980 to 2002 in the Nurses' Health Study and Nurses' Health Study II cohorts. We excluded subjects where SLE or RA was not confirmed by medical record review, and those who failed to return questionnaires. Semi-quantitative food frequency questionnaires assessed vitamin D intake from food and supplements. We used cumulative-updated total energy-adjusted dietary exposures for each 2-year cycle. Relationships between vitamin D intake and incident SLE and RA were examined in age-adjusted and Cox proportional hazards models, adjusted for confounders. Results were pooled using meta-analysis random effects models. RESULTS: We confirmed 190 incident cases of SLE and 722 of RA with dietary information. Increasing levels of vitamin D intake had no relationship to the relative risk of developing either SLE or RA. CONCLUSIONS: Vitamin D intake was not associated with risk of SLE or RA in these large prospective cohorts of women.

How CAM helps systemic lupus erythematosus.

The symptoms associated with systemic lupus erythematosus can vary in location and severity and often have life-altering effects. Because the disease is chronic, the use of traditional medical therapy may not bring about the maximum benefit in many cases. In light of this, many people diagnosed with lupus may turn to complementary and alternative medicine (CAM) therapies to help treat their disease. This article examines some of the common CAM methods used in addition to conventional medical treatment. Some points to consider include effectiveness, safety, cost, and ethical concerns associated with the use of CAM. The integration of these treatments into the medical regimen of those being treated for lupus is also considered.

Early hyperbaric oxygen therapy attenuates disease severity in lupus-prone autoimmune (NZB x NZW) F1 mice.

The effects of hyperbaric oxygen (HBO(2)) therapy on the immune system are reported including potential changes to the CD4/CD8 ratio and a decreased proliferation of lymphocytes during exposure. The immunosuppressive effect of HBO(2) had been suggested to be applicable for the treatment of certain autoimmune diseases. (NZB x NZW) F1 hybrid mice, the unique lupus-prone mice, have been used for elucidating the pathogenesis of SLE. To investigate the effect of HBO(2) on NZB/W F1 lupus-prone mice, 32 female mice were divided into four groups. Three groups of mice were treated with HBO(2) (2.5 atm abs (ATA) for 90 min daily over 2 weeks) starting at (A) 3 months, (B) 6 months, or (C) 8 months of age, while the remaining group (D) served as control. Animals were followed until 11 months of age. Experimental parameters included life span, proteinuria, peripheral lymphocytes, anti-dsDNA antibody titers, and renal histopathology. HBO(2) treatment resulted in increased survival, decreased proteinuria, alterations in lymphocyte-subset redistribution, reduced anti-dsDNA antibody titers, and amelioration of immune-complex deposition in groups A and B. Our data demonstrated that HBO(2) therapy attenuated disease severity in NZB/W F1 mice. HBO(2) treatment may be of use in the clinical treatment of lupus patients and would benefit from further study.

Inhibition of intracellular peroxides and apoptosis of lymphocytes in lupus-prone B/W mice by dietary n-6 and n-3 lipids with calorie restriction.

Our earlier studies have shown that calorie restriction and n-3 fatty acids inhibit autoimmune disease and prolong life span. Experiments were designed to study the alteration of apoptosis and its mediators in B/W mice fed either n-6 fatty acids [5% corn oil (CO)] or n-3 fatty acids [5% fish oil (FO)] and either allowed access to the diet ad libitum (AL) or restricted in caloric intake by 40% (CR), from 4 weeks of age. At 4 months (young) and 9 months (old) mice were killed, splenic lymphocytes were isolated, and apoptosis was measured with Annexin V and PI staining. Apoptosis was decreased in splenic lymphocytes from both young and old CR mice compared to their respective AL-fed control groups regardless of fat source. Increasing apoptosis with age was observed in CO/AL, CO/CR, and FO/AL mice which correlated closely with significantly higher cellular peroxides measured by flow cytometry using dichlorofluourescein diacetate (DCFH-DA), whereas in both CO/CR and FO/CR peroxide levels remained low in old mice. Furthermore, CR increased the proliferative response of splenic lymphocytes and decreased the Fas (CD95) and Fas-L protein expression in CD4+ lymphocytes from old mice. Higher levels of Fas and Fas-L expression were observed in old mice compared to young mice. Bcl-2 levels were elevated in both young and old CR groups compared to the respective AL groups. Calorie restriction prevented the loss of CD8 cells in old mice fed both the CO and the FO diet. In summary, CR resulted in decreased apoptosis accompanied by alterations in Fas, Fas-L, and Bcl-2 expression in old mice, increased life span, and delayed onset of kidney disease.

Diet modulates Th-1 and Th-2 cytokine production in the peripheral blood of lupus-prone mice.

Calorie restriction or fish oil extends life span. To investigate the potential mechanism(s) involved, young (4-month) and old (9-month) NZB x NZW(F1) mice were fed 5% (w/w) corn oil (CA) or fish oil (FA) ad libitum or 40% restricted (CR and FR, respectively). Peripheral blood T-lymphocytes were analyzed for Th-1 (IL-2, IFN-gamma) and Th-2 (IL-5, IL-10) production. CR and FA partially blunted while FR completely abolished the decline in aged CD4+ T lymphocytes. In contrast, both CR and FR abolished the decline in CD8+ T lymphocytes with age, while FA had no effect. In aged mice, both CR and FR blunted the increase in Th-1 (IL-2, IFN-gamma) cytokine production, while FA was only partially effective. Only FR completely blunted the age-related increase in Th-2 (IL-5, IL-10) cytokine production. These data suggest that FR delays the onset of autoimmune kidney disease by suppressing both Th-1 and Th-2 cytokine production.

Is there a case for DHEA replacement?

There are many hormonal changes that occur with ageing in humans, of which the most dramatic and intriguing change occurs for the adrenal androgenic steroid dehydroepiandosterone (DHEA). There are tantalizing epidemiological data demonstrating a significant association between the changes in circulating DHEA level and changes in the incidence of malignancy, atherosclerosis, Alzheimer's disease and other age-related changes. The pharmacological effects in animals such as rodents and rabbits have demonstrated many beneficial effects, for example increased immune function, the prevention of atherosclerosis, cancer, diabetes and obesity, and the improvement of memory. Clinical studies carried out in small groups of subjects have clearly demonstrated that the administration of DHEA to the elderly increases many hormone levels, including that of insulin-like growth factor-1, (free and total) testosterone, dihydrotestosterone, oestrone and oestradiol. It remains to be clearly defined whether these changes are clinically beneficial, and there is only insufficient information on the side-effects on long-term use. Results from short-term intervention studies in small groups of subjects have not demonstrated any convincing beneficial effects so far. A judgement on whether DHEA replacement has a place in preventing age-related disabilities could be determined only on the basis of results from studies of long-term DHEA replacement in elderly people.

Urtica dioica agglutinin, a V beta 8.3-specific superantigen, prevents the development of the systemic lupus erythematosus-like pathology of MRL lpr/lpr mice.

The V beta 8.3-specific superantigenic lectin Urtica dioica agglutinin (UDA) was used to delete the V beta 8.3+ T cells in MRL lpr/lpr mice. In contrast to the systemic lupus erythematosus-like pathology which progresses with age in the phosphate-buffered saline-injected MRL lpr/lpr controls, UDA-treated animals did not develop overt clinical signs of lupus and nephritis. The pathogenic T cell clones thus reside within the V beta 8.3+ T cell population, which includes an expanded T cell clone described previously. Finally, UDA alters the production of autoantibodies in a sex-dependent manner.