Periods Of Disease Activity Research Articles

EPIDEMIOLOGICAL AND CLINICAL EVOLUTIVE ASPECTS OF THE ULCERATIVE COLITIS. A 5-YEAR PROSPECTIVE STUDY IN A TERTIARY GASTROENTEROLOGY CENTER

INTRODUCTION: Over the last 3 decades, the improvement of diagnosis criteria in idiopathic inflammatory bowel diseases led to an increased interest on a global level for this pathology. The clinical evolution of the disease, the prognosis and any associated complications are of major importance for the patient and the treating physician. THE AIMS of the study has been to determine the epidemiological and clinical evolutive aspects of the patients with UC in a tertiary Gastroenterology center. MATERIAL AND METHOD. We have performed a prospective observational study on a batch of patients who were being monitored at our clinic in the period January 2007 – December 2011. The lot of study comprised 160 patients with UC. Each patient had a - patient’s record - in which we collected the demographic data, family history of inherited and collateral diseases, signs and symptomatology of the disease, the biological markers. There have been evaluated the extraintestinal and bowel complications, the treatment for each patient at the onset of the disease, during the active periods of the disease, and as well in the remission phase of the disease (clinical and endoscopic). RESULTS: The annual incidence of UC patients experienced an ascending trend from 12 newly diagnosed cases in 2007 to 35 new cases in 2010, respectively 30 new cases in 2011. Moreover, the number of monitored UC patients has increased from 58 in 2007 up to 160 in 2011. In the studied lot we had an approximate equal distribution on gender of the patients: 51% women, 49% men. Most of the patients were from of an active urban environment (71%). The minimum onset age of UC was 15, and the maximum age 80. 61% of the patients were non-smokers, and 25% active smokers. According to the extension of lesions, 60% of the patients had left-sided colitis, 22% extensive left-sided colitis, and 17% proctitis. According to the severity of the disease, 54% of the patients had moderate flares of disease, 24% mild flares, 15% severe flares and only 7% have been in clinical and endoscopical remission during the analyzed period. CONCLUSIONS: According to the results obtained UC has an ascending trend of incidence, fact that imposes an appropriate management of the patients with diarrheic syndrome to which there are associated or not pathologic elements (blood, mucus). These data demonstrate the usefulness of endoscopic monitoring in patients with an older dated disease and of those with an extensive form of the disease, including pancolitis, as well as the usefulness of early colectomy in patients with severe dysplasia. Keywords: Ulcerative colitis, Endoscopy, Colorectal cancer, Colectomy.

Thrombosis in vasculitis

To review the association of thrombosis and vasculitis and discuss some of the proposed causal mechanisms. It is becoming increasingly evident that various systemic inflammatory diseases such as vasculitis are associated with an increased risk of both venous and arterial thrombosis. Increasing evidence supports the use of immunosuppression in the management of venous thrombosis in Behçet's disease. An increased incidence of thromboembolic disease in antineutrophil cytoplasmic antibody-associated vasculitis has been recognized, especially during periods of active disease. In addition, a higher risk of ischemic heart disease in these patients has also been observed. As in giant cell arteritis, recent evidence supports the role of aspirin in the prevention of ischemic events in Takayasu's disease. Thromboembolic disease is an important complication of several forms of systemic vasculitis, and it may result in significant morbidity and mortality. Many questions such as the role for screening of asymptomatic patients, prevention of thrombosis, and duration of anticoagulation in patients with vasculitis remain unanswered. Future studies exploring the mechanisms of thrombosis and its link to inflammation may provide insights in predicting patients at a higher risk for thrombosis and improve outcomes.

A young woman with systemic lupus erythematosus and extensive mesenteric vasculitis involving small and medium vessels

History of the present illness The patient had 2 recent hospital admissions. Two months prior to her current presentation, she presented to the emergency department with a tooth abscess for which she underwent incision and drainage, and received a 1-week course of penicillin. One week later, she was admitted with a fever of 40.8°C and was noted to have tooth decay on panoramic radiographs without evidence of an abscess. She was treated with intravenous vancomycin and piperacillin tazobactam for 48 hours and then switched to oral clindamycin. Because of her elevated international normalized ratio (INR), she was unable to undergo tooth extraction prior to discharge. Two weeks later, she was readmitted with 4 days of recurrent fevers, malaise, diffuse arthralgias, and increased dyspnea with minimal exertion. Previous lupus exacerbations were characterized by arthralgias, rash, and hemolytic anemia. On this admission, laboratory evaluation revealed leukocytosis, worsening anemia and thrombocytopenia, creatinine of 0.7 mg/dl, alkaline phosphatase of 127 units/liter (normal value 111), spot urine proteinto-creatinine ratio of 1.47 (prior 1.1), low C3 and C4, and an increase in her double-stranded DNA by enzyme immunoassay from 120 to 768 IU/ml (normal value 30). She was empirically treated with vancomycin and piperacillin tazobactam given her recent tooth infection. The elevated alkaline phosphatase level prompted an abdominal ultrasound that showed multiple small hypoechoic areas in the spleen. An extensive infectious evaluation, including blood cultures, fungal serologies, knee arthrocentesis, magnetic resonance imaging of the lumbar spine, transthoracic and transesophageal echocardiograms, and computed tomography of the chest, abdomen, and pelvis, was negative. Her viral serologies were also unremarkable, other than evidence of IgG seropositivity for cytomegalovirus (CMV) with a negative viral load, consistent with prior exposure. Despite broad-spectrum antibiotics, she remained febrile. Her baseline prednisone dose of 12.5 mg was increased to 60 mg daily for possible lupus flare, after which she defervesced within 48 hours. Her thrombocytopenia was thought to be secondary to SLE-related idiopathic thrombocytopenic purpura because it resolved with high-dose steroids and intravenous immunoglobulin. She was discharged home 11 days after admission. The patient remained afebrile for 1 week at home. During this period she developed new-onset progressive upper abdominal pain with meals lasting 20–30 minutes. She denied associated constitutional symptoms, diarrhea, hematochezia, or melena.

Symptom burden: A forgotten area of measurement in inflammatory bowel disease

Inflammatory bowel disease (IBD) collectively known as Crohn's disease and ulcerative colitis are chronic inflammatory diseases of the digestive tract. Periods of active and inactive disease are common along the trajectory of this illness. A range of symptoms such as fatigue, diarrhoea and abdominal pain are experienced and are often very debilitating in nature resulting in significance interference in daily life. Despite this, to date, research in the area of symptoms remains an underexplored topic. This paper aims to discuss current approaches to symptom assessment in IBD and the potential to measure symptom burden in further research, in order to gain a greater understanding into the experiences of individuals with IBD.

Multi-Matrix System (MMX®) mesalamine for the treatment of mild-to-moderate ulcerative colitis

Introduction: Ulcerative colitis (UC) is an inflammatory disease of the colon characterized by periods of active disease and remission. The pathogenesis of this disease is likely a complex interaction of genetic predisposition, environmental factors, and immune system dysregulation, and is not completely understood. A Multi-MatriX (MMX®) system formulation of mesalamine, MMX mesalamine (SPD476; Lialda®; Mesavancol®; Mezavant®), allows for high-dose, once-daily dosing for patients with mild-to-moderate UC. Mesalamine is a topically active agent with anti-inflammatory properties.Areas covered: Available literature regarding MMX mesalamine is extensively reviewed in this article, covering its chemical makeup, mechanism of action, pharmaceutics and pharmacokinetics, clinical efficacy, and safety and tolerability.Expert opinion: A dose of 2.4 and 4.8 g was used in large Phase III clinical trials and was efficacious for induction of clinical and endoscopic remission in UC. MMX mesalamine was also efficacious in large multicenter maintenance studies for the maintenance of clinical and endoscopic remission. The introduction of the first once-daily mesalamine has given practitioners and patients more flexibility in dosing administration, which will ultimately lead to higher satisfaction and improved clinical outcomes.

Pediatric Systemic Lupus Erythematosus: More Than a Positive Antinuclear Antibody

Based on strong research evidence and consensus, the most common disease manifestations at diagnosis of pSLE are constitutional symptoms, arthritis, and malar rash. Based on some research evidence and consensus, patients with pSLE tend to have major organ system involvement (renal/central nervous system) and a greater disease burden compared with adults. Despite these findings, mortality is low. Based on some research evidence and consensus, the diagnosis of pSLE is unlikely if the ANA is negative, and most patients with SLE have a positive ANA at a titer ≥1:160. Based on strong research evidence, both MMF and cyclophosphamide can be used for induction therapy in class III and IV lupus nephritis. Based on strong research evidence, patients with SLE and anticardiolipin antibodies or LA have a two and six times greater risk of venous thrombosis, respectively, compared with patients with SLE without antiphospholipid antibodies. Based on strong research evidence, patients with pSLE have a higher risk for subclinical atherosclerosis when there is weight-adjusted prednisone use, azathioprine use, increasing age, male gender, high BMI, abnormal creatinine clearance, and elevated lipoprotein(a) levels.

Diagnostics in inflammatory bowel disease: ultrasound.

Diagnosis of chronic inflammatory bowel diseases (IBD) is based on a combination of clinical symptoms, laboratory tests and imaging data. Imaging of the morphological characteristics of IBD includes the assessment of mucosal alterations, transmural involvement and extraintestinal manifestations. No single imaging technique serves as a diagnostic gold standard to encompass all disease manifestations. Ultrasound, computed tomography (CT) or magnetic resonance imaging (MRI) allow cross-sectional imaging of the transmural alterations and extraintestinal manifestations. While in the USA the technique of choice is CT, in Europe the focus is more on MRI and ultrasound (US). Most patients with chronic IBD are diagnosed at a young age. After baseline diagnosis many of these young patients have to undergo repetitive imaging procedures during the variable clinical course of the disease, characterized by alternate periods of remission and active disease, and in monitoring the response to treatment. US has the advantage of being noninvasive, less costly, and easily repeatable, and thus can be very useful in following up patients with IBD. In addition, rising concern about radiation exposure in young adults indicates the demand for radiation-sparing techniques like US and MRI. This article focuses on the current clinical practice of US in IBD, describing the current technologies used in transabdominal intestinal US and the characteristic sonographic findings in Crohn´s disease and ulcerative colitis.

Holistic stoma care in support of patients with pseudomyxoma peritonei

Pseudomyxoma peritonei (PMP) is a rare but progressive condition that affects 1 in 1 million of the population. It is characterized by the excessive production of mucus within the abdominal and pelvic cavity, which left unchecked can have fatal consequences. Of those diagnosed with the condition a percentage will require a stoma. In this article, Carole Swash discusses how therapeutic support is achieved through holistic stoma care nursing during periods of active disease. In a case study, she explores the therapeutic role provided by the stoma care nurse (SCN) in dealing with the holistic needs of a patient with PMP.

Serum galectin‐3 levels in patients with Behçet’s disease: association with disease activity over a long‐term follow‐up

There is a need for a laboratory marker that correlates with the clinical activity of Behçet's disease (BD). We aimed to investigate whether serum galectin-3 (Gal-3) levels were affected during the course of the disease with regard to disease activity. A total of 131 subjects were involved in the study as follows: Group 1: BD active (n = 39); Group 2: BD inactive (n = 31); Group 3: Disease controls with leucocytoclastic vasculitis confirmed with a skin biopsy (n = 22); and Group 4: Healthy control subjects (n = 39). The BD patients were followed regularly and samples were taken in their active and inactive periods of the disease over a 2-year period. Serum Gal-3 levels were significantly higher in active BD patients (mean 2.38) than inactive BD patients (mean 0.63; P < 0.0001) and the healthy control subjects (mean 0.75; P < 0.0001). There was no significant difference between the leucocytoclastic vasculitis and active BD patients (P = 0.093). Serum Gal-3 levels were positively correlated with clinical activity scores of active BD patients (r = 0.66, P < 0.0001). In addition, the Gal-3 levels were significantly higher in the active disease period when compared with the inactive period during the follow-up. There were no significant differences between the two inactive periods of the disease among the same patients. Further analyses revealed that patients with vascular involvement had significantly higher Gal-3 levels than the other active BD patients (mean 7.57; P = 0.007). The limitation of the study is the small number of patients with vascular involvement in the active BD patient group. Gal-3 levels are correlated with the activity of Behçet's disease especially with the vascular involvement.

Should we fear “flu fear” itself? Effects of H1N1 influenza fear on ED use

BackgroundSurges in patient volumes compromise emergency departments' (EDs') ability to deliver care, as shown by the recent H1N1 influenza (flu) epidemic. Media reports are important in informing the public about health threats, but the effects of media-induced anxiety on ED volumes are unclear. ObjectiveThe aim of this study is to examine the effect of widespread public concern about flu on ED use. MethodsWe reviewed ED data from an integrated health system operating 18 hospital EDs. We compared ED visits during three 1-week periods: (a) a period of heightened public concern regarding flu before the disease was present (“Fear Week”), (b) a subsequent period of active disease (“Flu Week”), and (c) a week before widespread concern (“Control Week”). Fear Week was identified from an analysis of statewide Google electronic searches for “swine flu” and from media announcements about flu. Flu Week was identified from statewide epidemiological data. ResultsData were reviewed from 22 608 visits during the study periods. Fear Week (n = 7712) and Flu Week (n = 7687) were compared to Control Week (n = 7209). Fear Week showed a 7.0% increase in visits (95% confidence interval, 6-8). Pediatric visits increased by 19.7%, whereas adult visits increased by 1%. Flu Week showed an increase over Control Week of 6.6% (95% confidence interval, 6-7). Pediatric visits increased by 10.6%, whereas adult visits increased by 4.8%. ConclusionAt a time of heightened public concern regarding flu but little disease prevalence, EDs experienced substantial increases in patient volumes. These increases were significant and comparable to the increases experienced during the subsequent epidemic of actual disease.

Instruments to Measure Disease Activity in Systemic Lupus Erythematosus — Is Our Net Tight Enough to Catch the Hydra?

The Hydra of Greek mythology, a beast with multiple heads that grow again when cut off, has been suggested by Isenberg, et al 1 to be a model of systemic lupus erythematosus (SLE). In analogy with the Hydra, SLE can present itself in a multitude of guises, usually intermittently active, with sometimes abrupt flares, sometimes prolonged periods of active disease, as well as periods of clinical remission. However, there is always a risk that the disease will reappear. Active disease may cause organ damage, and disease activity over time has been shown to be strongly associated with mortality and organ damage2. Good instruments for monitoring disease activity, organ damage, and health status are required for adequate followup of longterm outcome and judgment of response to treatment. At every patient visit the physician should decide whether the patient’s disease is active and whether disease activity is the same, better, or worse compared with the previous visit. Further, annual assessment of organ damage and quality of life should be done to enable a complete evaluation of therapeutic response and prognostic considerations. A multitude of suggestions for disease activity assessment in SLE have been presented over … Address reprint request to Dr. Sturfelt; E-mail: Gunnar.Sturfelt{at}med.lu.se

Remission in Juvenile Idiopathic Arthritis: Current Facts

Juvenile idiopathic arthritis (JIA) is the most common chronic inflammatory arthritic disease affecting children. Despite the availability of potent disease-modifying antirheumatic medications, most children still experience a chronic course with long periods of active disease. Goals of treatment should include achievement of disease remission with optimal physical functioning that allows children to lead normal lives with no structural joint damage. The term remission implies a complete lack of disease activity. This article focuses on recently developed preliminary criteria for inactive disease and remission in JIA. Recent studies using these new definitions demonstrate only modest rates of achievement of remission favoring children with persistent oligoarticular JIA. Children with rheumatoid factor-positive polyarticular JIA are least likely to achieve remission. Therapeutic strategies to achieve remission are also discussed.

Persistent Hematuria After Induction of Remission in Wegener Granulomatosis

Wegener granulomatosis (WG) is a systemic disease that is often associated with an immune-mediated form of glomerulonephritis (GN). Renal disease most often manifests as microscopic hematuria with or without red blood cell or mixed cellular casts, proteinuria, and an elevated serum creatinine concentration.We conducted the current study to determine whether persistent hematuria, in the setting of apparent clinical remission, may reflect glomerular injury and not active renal disease. We performed a retrospective analysis of data from 82 patients with new-onset WG, of whom 25 had GN at presentation.Twenty of 25 patients with GN achieved sustained remissions (>6 consecutive months' duration). During initial periods of active disease the median peak serum creatinine was 1.9 mg/dL (range, 0.6-13.6 mg/dL). The median time to remission was 4 months (range, 2-13 mo). After effective therapy, median creatinine was 1.1 mg/dL (range, 0.4-1.8 mg/dL). Ten of 20 patients had prolonged hematuria over a period of >6 months. Within this subset, 5 subsequently normalized urine over a median period of 11 months and 5 did not achieve normal urine sediment over a median follow-up of 38 months. Thus, 10 of 25 patients with WG and GN had sustained hematuria in spite of apparent prolonged clinical remission.Patients with WG and GN may achieve enduring remissions that allow withdrawal of medications in spite of continued microscopic hematuria with or without red blood cell casts that may persist for months or even years. Continued use of aggressive immunosuppressive therapies in such patients would be ill-advised and could lead to irreversible and even life-threatening side effects from cyclophosphamide or high-dose corticosteroids.

Depression and anxiety in inflammatory bowel disease: A review of comorbidity and management

While there has been a great deal of speculation over the years on the importance of emotional factors in inflammatory bowel disease (IBD), it is only in the last decade or so that studies with stronger designs have been available to clarify the nature of this relationship. This review considers recent evidence on the prevalence of anxiety and depressive disorders in IBD, the role of these disorders as a risk factor for IBD onset, the degree to which they affect the course of the IBD, and the contribution of corticosteroid treatment to psychiatric symptom onset. There is evidence that anxiety and depression are more common in patients with IBD and that the symptoms of these conditions are more severe during periods of active disease. The few studies that address the issue of anxiety and depression as risk factors for IBD do not yet provide enough information to support definite conclusions. There is evidence, however, that the course of the disease is worse in depressed patients. Treatment with corticosteroids can induce mood disorders or other psychiatric symptoms. The second part of the review focuses on patient management issues for those with comorbid anxiety or depression. Practical approaches to screening are discussed, and are recommended for routine use in the IBD clinic, especially during periods of active disease. We review evidence-based pharmacological and psychological treatments for anxiety and depression and discuss practical considerations in treating these conditions in the context of IBD to facilitate overall management of the IBD patient.

Thromboembolic disease in vasculitis

To give an overview of recent clinical findings of thromboembolic disease in vasculitis and provide insight into possible explanations of the association between thrombosis and inflammation. A high incidence of venous thrombotic events has recently been described in four distinct cohorts of patients with antineutrophil cytoplasmic antibody-associated vasculitis (AAV), especially during periods of active disease. No factors other than the vasculitis itself have been identified that explain this high occurrence of thrombosis. Several studies have shown an increased rate of thrombosis in Behçet's disease, with a different clinical presentation from that observed in AAV. Recent laboratory findings provide exciting insights into a bidirectional feedback loop between coagulation and inflammation that may be applicable to vasculitis. Thrombosis is an important clinical manifestation of some types of vasculitis. Better understanding of the association of thrombosis with inflammation in vasculitis might lead to development of clinically useful biomarkers and new approaches to therapy. Additionally, study of the specific factors involved in thrombosis in systemic vasculitis could help explain the role of inflammation in more common settings of venous thrombotic events.

Long-term natural history of Crohn’s disease

Crohn's disease is a chronic inflammatory granulomatous process that usually involves different sites in the intestinal tract. Genetic and environmental factors are thought to play a role in its etiology and pathogenesis. The disorder has a heterogeneous clinical expression and data from tertiary care settings have documented its female predominance, occasional familial nature, and high rate of stricture formation and penetrating disease. It may appear from early childhood to late adulthood, although over 80% are currently diagnosed before age 40 years, usually with terminal ileal and colonic involvement. Several studies have now shown differences in phenotypic clinical expression depending on the initial age at diagnosis, with pediatric-onset disease being more severe and more extensive with more involvement of the upper gastrointestinal tract compared to adult-onset disease. In addition, long-term studies from these tertiary care settings have documented that the disorder may evolve with time into a more complex disease with stricture formation and penetrating disease complications (i.e. fistula and abscess). Although prolonged remission with no evidence of inflammatory disease may occur, discrete periods of symptomatic and active granulomatous inflammatory disease may re-appear over many decades. Long-term studies on the natural history have also suggested that discrete events (or agents) may precipitate this granulomatous inflammatory process.

Lipid changes occuring in the course of hematological cancers

The relationship between plasma lipid levels and mortality from cardiovascular diseases has been shown in many studies, but there has been far less investigation into their relationship to non-cardiovascular diseases. The aim of this study was to investigate the lipid profile of individuals with hematological malignancies and its relationship to disease activity. 238 patients were included in the study: 84 with acute leukemia, 62 with non-Hodgkin lymphoma, 35 with Hodgkin’s lymphoma, 32 with multiple myeloma, and 25 with myeloproliferative syndrome. The HDL cholesterol level of the patients differed to that of the individuals in the control group in the active disease period for all the analyzed disorders, but only remained statistically significant in the acute leukemia and non-Hodgkin lymphoma groups during the remission period. Smaller differences were observed for the remaining lipid fractions, except for the triglyceride level, which increased in the active disease period in all the analyzed disorders except non-Hodgkin lymphoma. The most pronounced changes in the lipid fractions occurred in the HDL cholesterol level, and were the most remarkable for acute leukemia.

Responsiveness of exercise parameters in children with inflammatory myositis

Juvenile dermatomyositis (DM) is an inflammatory myopathy in which the immune system targets the microvasculature of the skeletal muscle and skin, leading to significant muscle weakness and exercise intolerance, although the precise etiology is unknown. The goal of this study was to investigate the changes in exercise capacity in children with myositis during active and inactive disease periods and to study the responsiveness of exercise parameters. Thirteen children with juvenile DM (mean+/-SD age 11.2+/-2.6 years) participated in this study. Patients performed a maximal exercise test using an electronically braked cycle ergometer and respiratory gas analysis system. Exercise parameters were analyzed, including peak oxygen uptake (VO2peak), peak work rate (Wpeak), and ventilatory anaerobic threshold (VAT). All children were tested during an active period of the disease and during a remission period. From these data, 4 different response statistics were calculated. The children performed significantly better during a remission period compared with a period of active disease. Most exercise parameters showed a very large response. The 5 most responsive parameters were Wpeak, Wpeak (percent predicted), oxygen pulse, VO2peak, and power at the VAT. We found in our longitudinal study that children with active juvenile DM had significantly reduced exercise parameters compared with a remission period. Moreover, we found that several parameters had very good responsiveness. With previously established validity and reliability, exercise testing has been demonstrated to be an excellent noninvasive instrument for the longitudinal followup of children with myositis.

Antiproteinase 3 Antineutrophil Cytoplasmic Antibodies and Disease Activity in Wegener Granulomatosis

The utility of antineutrophil cytoplasmic antibody (ANCA) levels to guide the management of patients with Wegener granulomatosis remains controversial. To determine whether pro-proteinase 3 (PR3)-ANCA levels are a better measure of disease activity than mature-PR3-ANCA levels, whether decreases in either level are associated with shorter time to remission, and whether increases are followed by relapse. Prospective, observational cohort study. 8 United States medical centers that participated in a treatment trial for Wegener granulomatosis. 156 patients with Wegener granulomatosis enrolled during periods of active disease. PR3-ANCA levels (by capture enzyme-linked immunosorbent assay) and disease activity (by the Birmingham Vasculitis Activity Score for Wegener granulomatosis). The ANCA levels were only weakly associated with disease activity across patients. The longitudinal association within patients was stronger, but changes in ANCA levels explained less than 10% of the variation in disease activity. Decreases in mature- and pro-PR3-ANCA levels were not statistically significantly associated with shorter time to remission, and increases in mature-PR3-ANCA levels (adjusted hazard ratio, 0.8 [95% CI, 0.4 to 1.9]; P = 0.67) and pro-PR3-ANCA levels (adjusted hazard ratio, 1.0 [CI, 0.5 to 2.1]; P = 0.99) were not associated with relapse. The proportion of patients who had relapse within 1 year of an increase in PR3-ANCA levels was 40% for mature-PR3 (CI, 18% to 56%) and 43% for pro-PR3 (CI, 22% to 58%). Samples were collected approximately every 3 months. Sensitivity and specificity of ANCA levels for detecting remission and relapse could not be calculated because each patient had different follow-up times. Pro-PR3-ANCA is no better than mature-PR3-ANCA as a measure of Wegener granulomatosis activity. Decreases in PR3-ANCA levels are not associated with shorter time to remission, and increases are not associated with relapse. These findings suggest that ANCA levels cannot be used to guide immunosuppressive therapy.

Effect of DAB389IL-2 immunotoxin on the course of experimental autoimmune encephalomyelitis in Lewis rats

Activated T cells express the high affinity interleukin 2 receptor (IL-2R also CD25) that binds interleukin 2 (IL-2) and transduces signals important for the proliferation and survival of these cells. We investigated the effect of the genetically engineered immunotoxin DAB(389)IL-2 on experimental autoimmune encephalomyelitis (EAE), an autoimmune disease of the central nervous system (CNS) mediated by activated myelin-reactive T cells. EAE is the most commonly used animal model of the human disease multiple sclerosis (MS). DAB(389)IL-2 is a recombinant fusion product made of a portion of diphtheria toxin, which contains binding and translocation components of the toxin linked to IL-2. The diphtheria toxin targets and kills cells expressing the high affinity IL-2 receptor and has been successfully used in several autoimmune and neoplastic conditions. We observed a significant suppression of guinea-pig spinal cord homogenate (gpSCH)-MBP induced active EAE in Lewis rats at 2 x 1,600 kU of DAB(389)IL-2 given on days 7 and 9 post-immunization and complete suppression with the same dose on days 7, 8 and 9 or 7, 8, 9 and 10 after immunization during the active disease period. There were reduced mononuclear cell infiltrates of CD4(+), CD8(+), CD25(+) and alphabetaTCR(+) T cells in the spinal cord of treated rats. However, treatment at day 11 or 12 post-immunization led to severe, fatal disease. The toxin added to cultures in vitro or injected in vivo suppressed antigen- and mitogen-induced T cell proliferation. DAB(389)IL-2 treatment in vivo or exposure of encephalitogenic T cells in vitro prior to transfer did have a significant inhibitory effect on adoptive transfer EAE. Our data demonstrate that DAB(389)IL-2 immunotoxin can suppress active and passive EAE if applied at specific, early time points, but can have negative consequences at later time points.