Tratamiento con tocilizumab en amiloidosis AA: informe de casos y revisión de la literatura / Tocilizumab treatment in aa amyloidosis: case report and literature review

Introducción: la amiloidosis AA puede ser una complicación de ciertos trastornos inflamatorios crónicos, aunque entre el 21% y 50% puede ser idiopática. No existe un tratamiento específico. El tocilizumab, dirigido contra el receptor de IL-6 y orientado a disminuir la producción de SAA, podría ser eficaz. Métodos: en este estudio informamos datos de 6 pacientes con amiloidosis AA tratados con tocilizumab monoterapia subcutáneo en el período 2011-2018. Los criterios de valoración principales fueron la mejora clínica y bioquímica de los órganos afectados y los parámetros bioquímicos marcadores de inflamación. Resultados: el riñón estaba afectado en todos los pacientes, manifestándose con caída del filtrado glomerular y síndrome nefrótico. La hemorragia digestiva se presentó en un paciente y otro tenía afectación pulmonar en la biopsia. Luego del posterior al tratamiento, todos mejoraron el hematocrito, la albúmina sérica y el índice de masa corporal. El SAA disminuyó en 5 pacientes. Un paciente mejoró su función renal, mientras 4 se mantuvieron estables. Tres pacientes disminuyeron los valores de proteinuria. Conclusión: el tratamiento con tocilizumab podría ser eficaz en el tratamiento de los pacientes con amiloidosis AA. (AU)

Introduction: AA amyloidosis can be a complication of certain chronic inflammatory disorders, although between 21% and 50% can be idiopathic. There is no specific treatment. Tocilizumab, directed against the IL-6 receptor and aimed at decreasing SAA production, could be effective. Methods: in this study, we report data from 6 patients with AA amyloidosis treated with subcutaneous tocilizumab monotherapy between the period 2011-2018. The main endpoints were the clinical and biochemical improvement of the affected organs and the biochemical parameters markers of inflammation. Results: the kidney was affected in all patients, manifesting with a fall in glomerular filtration rate and nephrotic syndrome. Gastrointestinal bleeding occurred in one patient and another had lung involvement on biopsy. After treatment, all improved hematocrit, serum albumin, and body mass index. SAA decreased in 5 patients. One patient improved his kidney function, while 4 remained stable. Three patients decreased proteinuria values. Conclusion: treatment with tocilizumab could be effective in the treatment of patients with AA amyloidosis. (AU)

Down-regulation of the inflammatory response after short-term exposure to low levels of chemical vapours.

OBJECTIVE: To investigate the relation between signs and symptoms of irritation and biomarkers of inflammatory markers in blood in healthy volunteers exposed to different chemical vapours for 2 or 4 hours in an exposure chamber. METHODS: The investigated chemicals were: acetic acid (5 and 10 ppm), acrolein (0.05 and 0.1 ppm), 1,4-dioxane (20 ppm), n-hexanal (2 and 10 ppm), hydrogen peroxide (0.5 and 2.2 ppm), 2-propanol (150 ppm), m-xylene (50 ppm), standard and dearomatised white spirit (100 and 300 mg/m3). C reactive protein (CRP), serum amyloid A protein and interleukin 6 were measured in plasma immediately before and 2 or 4 hours after the exposures. Symptoms were rated from 0 to 100 mm in Visual Analogue Scales and covered 10 questions whereof four related to irritation: discomfort in the eyes, nose and throat and dyspnoea. The effect measurements included blink frequency by electromyography, nasal swelling by acoustic rhinometry and lung function by spirometry. RESULTS: Logistic quantile regression analyses revealed no significant associations except a negative relation between ratings of irritation and CRP. CONCLUSION: The results suggest a down-regulation of CRP after short-term exposure to low levels of vapours of irritating chemicals. This response might be mediated by the cholinergic anti-inflammatory pathway and further studies are recommended in order to refute or confirm this hypothesis.

Emerging treatments for amyloidosis.

Amyloidosis results from protein misfolding, and ongoing amyloid deposition can ultimately lead to organ failure and death. Historically, this is a group of diseases with limited treatment options and frequently poor prognosis. However, there are now 'targeted' therapeutics emerging in the form of stabilizers of the precursor protein, inhibitors of fibrillogenesis, fibril disruptors, and blockers of protein translation, transcription, and immunotherapy. We review many of these approaches that are currently being assessed in clinical trials.

Periodontal and serum protein profiles in patients with rheumatoid arthritis treated with tumor necrosis factor inhibitor adalimumab.

BACKGROUND: Tumor necrosis factor (TNF)-α inhibitor has been shown to affect the periodontal condition of patients with rheumatoid arthritis (RA). The aim of the present study is to assess the effect of a fully humanized anti-TNF-α monoclonal antibody, adalimumab (ADA), on the periodontal condition of patients with RA and to compare serum protein profiles before and after ADA therapy. METHODS: The study participants consisted of 20 patients with RA treated with ADA. Clinical periodontal and rheumatologic parameters and serum cytokine levels were evaluated at baseline and 3 months later. Serum protein spot volume was examined with two-dimensional sodium dodecyl sulfate polyacrylamide gel electrophoresis. Proteins with significant difference in abundance before and after ADA therapy were found and identified using mass spectrometry and protein databases. RESULTS: The patients showed a significant decrease in gingival index (P = 0.002), bleeding on probing (P = 0.003), probing depth (P = 0.002), disease activity score including 28 joints using C-reactive protein (P <0.001), and serum levels of TNF-α (P <0.001) and interleukin-6 (P <0.001) after ADA medication, although plaque levels were comparable. Among a total of 495 protein spots obtained, nine spots were significantly decreased in abundance at reassessment, corresponding to complement factor H, phospholipase D, serum amyloid A, complement component 4, and α-1-acid glycoprotein (P <0.01). CONCLUSION: These results suggest a beneficial effect of ADA therapy on the periodontal condition of patients with RA, which might be related to differences in serum protein profiles before and after ADA therapy.

Salvianolic acid A, a polyphenolic derivative from Salvia miltiorrhiza bunge, as a multifunctional agent for the treatment of Alzheimer's disease.

The effects of Salvianolic acid A (Sal A) on the treatment of Alzheimer's disease (AD) were investigated. Sal A significantly inhibits amyloid beta [Formula: see text] self-aggregation and disaggregates pre-formed [Formula: see text] fibrils, reduces metal-induced [Formula: see text] aggregation through chelating metal ions, and blocks the formation of reactive oxygen species (ROS) in SH-SY5Y cells. Sal A protects cells against [Formula: see text]-induced toxicity. Furthermore, Sal A, possibly because of the effects of decreasing toxicity effects of [Formula: see text] species, alleviates [Formula: see text]-induced paralysis in transgenic Caenorhabditis elegans. Circular dichroism (CD) experiments and Molecular dynamic (MD) simulations demonstrate that Sal A inhibits [Formula: see text] self-aggregation through binding to the C-terminus of [Formula: see text], and therefore stabilizing the [Formula: see text]-helical conformations. Altogether, our data show that Sal A, as the multifunctional agent, is likely to be promising therapeutics for AD.

Ibuprofen inhibits the synaptic failure induced by the amyloid-ß peptide in hippocampal neurons.

Epidemiological studies have reported a decrease in the prevalence of Alzheimer's disease in individuals who chronically use non-steroidal anti-inflammatory drugs (NSAIDs). Clinical trials, on the other hand, have been less positive. Nevertheless, it has been proposed that NSAIDs exert part of their effects by reducing long-term cerebral neuroinflammation, although this mechanism has not been proven. In this study, we report that ibuprofen, one of the more widely used non-steroidal anti-inflammatory drugs, was able to alter the ultrastructure of amyloid-ß peptide (Aß) and significantly decrease its association to neuronal membranes, and consequently, its synaptotoxic effect in rat primary hippocampal and cortical cultures at 24 h incubation. In agreement with these results, we found that the decrease in the frequency of calcium transients with Aß was partly recovered by addition of ibuprofen (8.0 × 10-2 Hz in control; 3.4 × 10-2 Hz in 5 µM Aß, and 5.9 × 10-2 Hz in the presence of Aß and 200 µM ibuprofen). Additionally, this effect correlated well with the increment and recovery of miniature spontaneous currents (47 ± 5% of control in 1 µM Aß alone and 104 ± 14% in the presence of Aß and ibuprofen). Our results suggest that ibuprofen could be exerting its neuroprotective effect by directly interacting with Aß and altering its toxic aggregated forms. We postulate that other ibuprofen analogs with better pharmacological properties might have a higher efficacy in AD.

Effects of l-carnitine supplement on serum amyloid A and vascular inflammation markers in hemodialysis patients: a randomized controlled trial.

OBJECTIVE: We studied the effects of l-carnitine supplement on serum amyloid A (SAA), a systemic inflammation marker, and vascular inflammation markers in hemodialysis patients. DESIGN: This was a randomized, double-blind, placebo-controlled trial. SETTING: The study was performed in Soodeh Hemodialysis Center in Islamshahr, Iran. PATIENTS: We included 36 hemodialysis patients (15 men and 21 women). INTERVENTION: The patients on hemodialysis were randomly assigned to either a carnitine or a placebo group. Patients in the carnitine group received 1,000 mg/day oral l-carnitine for 12 weeks, whereas patients in the placebo group received a corresponding placebo during the study. MAIN OUTCOME MEASURES: Serum free carnitine, SAA, soluble intercellular adhesion molecule type 1, soluble intercellular adhesion molecule type 2, soluble vascular cell adhesion molecule type 1, sE-selectin, sP-selectin, and oxidized low-density lipoprotein were measured at baseline and at the end of week 12 of the study. RESULTS: Mean serum free carnitine concentration increased significantly to 150% of baseline in the carnitine group at the end of week 12 (P < .001), whereas serum SAA showed a significant 32% decrease (P < .001). No significant changes were observed in the serum concentrations of free carnitine and SAA in the placebo group during the study. There were no significant differences between the two groups in mean changes in serum soluble intercellular adhesion molecule type 1, soluble intercellular adhesion molecule type 2, soluble vascular cell adhesion molecule type 1, sE-selectin, sP-selectin, and oxidized low-density lipoprotein concentrations. CONCLUSION: The study indicates that l-carnitine supplement reduces serum SAA, which is a risk factor for cardiovascular diseases in hemodialysis patients, but has no effect on vascular inflammation markers.

Influence of long-term leflunomide treatment on serum amyloid concentration in rheumatoid arthritis patients.

Rheumatoid arthritis (RA) is a chronic, inflammatory disease that requires intervention with disease-modifying antirheumatic drugs (DMARDs) to stop disease progression. Leflunomide (LEF) is a DMARD with anti-inflammatory and immunomodulatory properties. As its primary mode of action, LEF reversibly inhibits dihydroorotate dehydrogenase, a key enzyme in de novo biosynthesis of pyrimidine in cells. Serum amyloid A protein (SAA) is elevated in inflammatory states and high SAA levels indicate a risk of developing secondary amyloidosis. The aim of this study was to investigate the effects of long-term LEF treatment on SAA levels and disease activity in a group of RA patients. The study group consisted of 50 consecutive RA patients (43 F, 7 M) treated with leflunomide. All patients had a clinical evaluation and SAA measurements taken at two consecutive visits during months 0, 1, 3, 6 and 12. Mean SAA concentrations decreased significantly in the first months of LEF therapy (up to the 6th month) with a more pronounced effect in patients with higher SAA levels. However, by the 12(th) month of treatment, the mean SAA level did not differ significantly from the SAA level at the start of treatment. At the same time though, other clinical and laboratory parameters of RA activity indicated that the disease activity decreased. Results demonstrated that in patients with active RA LEF therapy provided a significant, long-term reduction of inflammatory activity, as measured by the classic parameters of disease activity. During the treatment, SAA concentrations decreased significantly, followed by a slight increase, in spite of a reduction in other classical indicators of inflammatory response.

Standardized capsule of Camellia sinensis lowers cardiovascular risk factors in a randomized, double-blind, placebo-controlled study.

OBJECTIVE: Previous studies examining the effect of tea drinking on cardiovascular health have produced mixed results due to their observational nature and qualitatively and quantitatively imprecise definitions of active tea components. The objective of this study was to determine if a standardized and defined decaffeinated green tea (Camellia sinensis) product lowers blood pressure, serum lipids, oxidative stress, and markers of chronic inflammation. METHODS: A randomized, double-blind, placebo-controlled, parallel study on 111 healthy adult volunteers 21-70 y old was performed. We administered a standardized capsule of Camellia sinensis compounds (CSC) twice a day. Before and after 3 wk, blood pressure, serum lipids, serum amyloid-alpha (a marker of chronic inflammation), and serum malondialdehyde (a marker of oxidative stress) were measured. RESULTS: After 3 wk, CSC lowered systolic and diastolic blood pressures by 5 and 4 mmHg, respectively. After 3 mo, systolic blood pressure remained significantly lower. CSC lowered serum amyloid-alpha by 42% and lowered malondialdehyde by 11.9%. In men, there were 10- and 9-mg/dL reductions in total and low-density lipoprotein (LDL) cholesterol, respectively. In all subjects with a baseline LDL cholesterol level >99 mg/dL, there was 9 mg/dL lowering of total and LDL cholesterol. Adverse effects were mild and few and not different from placebo. CONCLUSION: CSC was effective for decreasing, in as quickly as 3 wk, blood pressure, LDL cholesterol, oxidative stress, and a marker of chronic inflammation, all independent cardiovascular risk factors.

Therapeutic effects of triptolide on interleukin-10 gene-deficient mice with colitis.

BACKGROUND: Triptolide, the principal active ingredient in the extract of Chinese herb Tripterygium wilfordii Hook , has both anti-inflammatory and immunomodulatory activities. However, the potential therapeutic role of triptolide in IBD was still unknown. Interleukin-10 deficient mice, a well characterized experimental model of inflammatory bowel disease, spontaneously developed a Th1 T cell-mediated colitis with many similarities to Crohn's disease. This study was designed to investigate the therapeutic effect of triptolide on the chronic colitis in IL-10-/- mice. METHODS: Triptolide was intraperitoneally administrated every another day for 8 weeks to IL-10-/- mice. The gross and histological appearances of the colon, the level of inflammatory mediators and transcription factor activation in the colon were evaluated and compared with the control group. RESULTS: The 8-week administration of triptolide resulted in a significant decrease in the severity of colitis, together with lower production of TNF-alpha ,IFN-gamma and IL-4 in colon. The level of serum amyloid A was decreased in triptolide-treated mice. Gene expressions of IL-12 and IL-23 in colon were also downregulated after treatment. Furthermore, administration of triptolide markedly reduced NF-small ka, CyrillicB activation in colon mucosa of IL-10-/- mice. CONCLUSIONS: The efficacy of tritpolide treatment for the reduction of intestinal inflammation in IL-10-/- mice is a result of both anti-inflammatory and immunosuppressive activity. Triptolide holds significant potential for clinical applications for CD treatment.

Inflammation, statin therapy, and risk of stroke after an acute coronary syndrome in the MIRACL study.

OBJECTIVE: Patients with acute coronary syndromes have an increased risk of stroke. We measured markers of inflammation in the MIRACL study, a randomized trial of atorvastatin versus placebo in acute coronary syndromes, to assess the relationship of inflammation to stroke. METHODS AND RESULTS: Baseline C-reactive protein (CRP), serum amyloid A (SAA), and interleukin-6 (IL-6) were collected in 2926 (95%) subjects. Baseline markers were related to stroke risk over the 16 weeks of the study. Subjects who subsequently experienced a stroke had higher CRP (27.5 versus 10.2 mg/L, P=0.0032), SAA (30.5 versus 16.0 mg/L, P=0.031), IL-6 (11 231 versus 6841 pg/L, P=0.004), and troponin (6.03 versus 3.19 ng/mL P=0.0032). The risk of stroke was related to greater CRP, SAA, and IL-6 in the placebo group only. Similarly, there was a graded increase in risk of stroke across quartiles of inflammatory markers in the placebo patients only. CONCLUSIONS: In acute coronary syndromes, the early risk of stroke relates to both heightened inflammation and size of myocardial necrosis. Treatment with atorvastatin abrogated the risk associated with elevated markers of inflammation in this study, a finding that provides a novel rationale for the use of statins in acute coronary syndromes.

Eprodisate for the treatment of renal disease in AA amyloidosis.

BACKGROUND: Amyloid A (AA) amyloidosis is a complication of chronic inflammatory conditions that develops when proteolytic fragments of serum amyloid A protein (SAA) are deposited in tissues as amyloid fibrils. Amyloid deposition in the kidney causes progressive deterioration in renal function. Eprodisate is a member of a new class of compounds designed to interfere with interactions between amyloidogenic proteins and glycosaminoglycans and thereby inhibit polymerization of amyloid fibrils and deposition of the fibrils in tissues. METHODS: We performed a multicenter, randomized, double-blind, placebo-controlled trial to evaluate the efficacy and safety of eprodisate in patients with AA amyloidosis and kidney involvement. We randomly assigned 183 patients from 27 centers to receive eprodisate or placebo for 24 months. The primary composite end point was an assessment of renal function or death. Disease was classified as worsened if any one of the following occurred: doubling of the serum creatinine level, reduction in creatinine clearance by 50% or more, progression to end-stage renal disease, or death. RESULTS: At 24 months, disease was worsened in 24 of 89 patients who received eprodisate (27%) and 38 of 94 patients given placebo (40%, P=0.06); the hazard ratio for worsening disease with eprodisate treatment was 0.58 (95% confidence interval, 0.37 to 0.93; P=0.02). The mean rates of decline in creatinine clearance were 10.9 and 15.6 ml per minute per 1.73 m(2) of body-surface area per year in the eprodisate and the placebo groups, respectively (P=0.02). The drug had no significant effect on progression to end-stage renal disease (hazard ratio, 0.54; P=0.20) or risk of death (hazard ratio, 0.95; P=0.94). The incidence of adverse events was similar in the two groups. CONCLUSIONS: Eprodisate slows the decline of renal function in AA amyloidosis. (ClinicalTrials.gov number, NCT00035334.)

Involvement of M1-muscarinic acetylcholine receptors, protein kinase C and mitogen-activated protein kinase in the effect of huperzine A on secretory amyloid precursor protein-alpha.

This study is to explore the involvement of muscarinic acetylcholine receptors/protein kinase C cascade and the mitogen-activated protein kinase pathway in the effect of huperzine A on the secretory amyloid precursor protein-alpha. Upregulation of secretory amyloid precursor protein-alpha by huperzine A was attenuated by muscarinic acetylcholine receptor antagonist (specifically by M1-muscarinic acetylcholine receptor antagonist), and markedly blocked (-37.7%) by protein kinase C inhibitor as well. Meanwhile, huperzine A can activate the phosphorylation of mitogen-activated protein kinase and, accordingly, partly restored PD98059-decreased secretory amyloid precursor protein-alpha secretion. In addition, huperzine A largely inhibited (-55.4%) acetylcholinesterase activity of the cell line. Our results suggest that activated M1-muscarinic acetylcholine receptor/protein kinase C pathway and mitogen-activated protein kinase signaling are involved in the process of huperzine A enhancing the secretory amyloid precursor protein-alpha secretion.

Beneficial effects of angiotensin II type 1 receptor blocker antihypertensive treatment on inflammation indices: the effect of smoking.

The effect of long-term angiotensin II type 1 receptor blocker (ARB) therapy on inflammation indices has not been fully investigated in a hypertensive population. The authors evaluated 323 consecutive nondiabetic patients (mean age, 57 years; 176 men; 92 smokers) with high renin activity and uncomplicated essential hypertension whose blood pressure levels normalized (from 163.9/100.7 mm Hg to 131.6/82.8 mm Hg) after 4 weeks of ARB or ARB/diuretic treatment. All patients underwent full laboratory evaluation (routine examination of blood and urine, liver, kidney, thyroid function, and lipid and glucose profiles), including measurement of high-sensitivity C-reactive protein and serum amyloid A levels, at drug-free baseline, which was repeated after 6 months of ARB or ARB/diuretic treatment. A significant (P<.001) overall decrease was noted in both high-sensitivity C-reactive protein (-0.41+/-1.56 mg/dL) and serum amyloid A (-0.62+/-2.03 mg/dL), but a smaller decrease in high-sensitivity C-reactive protein and serum amyloid A change was seen in the smoker subgroup compared with nonsmokers (P<.05), indicating that the ARB or ARB/diuretic anti-inflammatory effect may be adversely affected by smoking status.

FK506 inhibits murine AA amyloidosis: possible involvement of T cells in amyloidogenesis.

OBJECTIVE: To determine the possibility that T cells represent a potential target for therapy in AA amyloidosis. METHODS: AA amyloidosis was induced in C3H/HeN mice by concomitant administration of AgNO3 and amyloid-enhancing factor (AEF). Mice injected with AgNO3 and AEF received intraperitoneal injections of FK506 (2-200 microg/day). The degree of splenic amyloid deposition was determined by Congo red staining. Serum amyloid A (SAA), interleukin 1beta (IL-1beta), IL-6, and tumor necrosis factor-a concentrations were measured by ELISA. AA amyloidosis was also induced in ICR mice by injection of Freund's complete adjuvant (FCA) and Mycobacterium butyricum without AEF. ICR mice injected with FCA and M. butyricum also received intraperitoneal injections of FK506 (200 microg/day) to eliminate the possibility that FK506 action might depend upon AEF activity in the amyloid formation. Amyloid deposition was also induced with and without AEF in severe combined immunodeficient (SCID) mice and nude mice to clarify the role of T cells in the mechanism of amyloid formation in AA amyloidosis. RESULTS: FK506 treatment significantly reduced the amount of amyloid deposition and incidence of amyloidosis without reducing serum SAA and proinflammatory cytokine levels in the murine AA amyloidosis models with and without AEF. SCID mice and nude mice showed resistance to development of AA amyloidosis. CONCLUSION: Our findings may provide a new therapeutic strategy for amyloidosis. The results suggested that T cells may play an important role in the mechanism of amyloid formation in AA amyloidosis.

Transdermal photodynamic therapy--a treatment option for rheumatic destruction of small joints?

BACKGROUND AND OBJECTIVE: Synovectomy of small joints is a therapeutic approach in patients suffering from rheumatoid arthritis (RA). We examined the feasibility of transdermal photodynamic therapy (tPDT) in a fibroblast-induced model of joint destruction using the novel photosensitizer (PS) tetrahydroporphyrin-tetratosylat that shows strong absorption at the near infra-red spectral region. MATERIALS AND METHODS: The functionality of the PDT system was assessed in vitro. Following arthritis induction and PS application, tPDT was applied in vivo. Therapy results were evaluated by measuring joint swelling, serum amyloid A (SAA) and histologically. RESULTS: We were able to present a fully functional PDT in vitro. The in vivo therapy modalities were well tolerated by mice. We could demonstrate photodynamic ablation of subcutaneously located tissue (skeletal muscle) without skin damage. CONCLUSION: This study provides the basis for transdermal accessibility of tissue through a photodynamic process which may serve as a minimally invasive synovectomy strategy.

Efficacy of a transforming growth factor beta 2 containing nutritional support formula in a murine model of inflammatory bowel disease.

OBJECTIVE: Dietary, environmental and genetic events may influence host susceptibility to inflammatory bowel diseases (IBD). Transforming growth factor beta 2 (TGF-beta 2), a multifunctional polypeptide (cytokine) present in human and bovine milk, plays a critical role in the development of tolerance, the prevention of autoimmunity, and in anti-inflammatory responses. TGF-beta 2 is a potent inhibitor of intestinal epithelial cell (IEC) growth and stimulates IEC differentiation. The objective of this study was to determine whether a diet containing TGF-beta 2 modulates intestinal injury and immune responses in an Interleukin-10 knockout (IL-10-/-) mouse model of IBD. METHODS: Five-week-old IL-10-/- mice (in BALB/c background) reared in our transgenic facility were fed either an enteral diet (Diet-A) containing TGF-beta 2 or a control enteral diet (Diet-B) not rich in TGF-beta 2. Mice were weighed weekly, monitored for illness and euthanized after eight weeks on the diet. RESULTS: Final weights were 28 +/- 1.2 g (58.2% gain) for Diet-A mice and 23 +/- 1.6 g (32.9% gain) for Diet-B mice (p = 0.0194). The hematocrits were 48.3% for Diet-A compared to 42% for Diet-B mice (p = 0.0021). Mice on Diet-A had significantly lower serum TNF-alpha concentrations. Forty-four percent of mice on Diet-B developed severe diarrhea and rectal prolapse compared with none on Diet-A. Evaluation of intestinal pathology (score 0-4) revealed that animals fed Diet-A had a score of 2.1 +/- 0.4 compared to 3.2 +/- 0.36 in the Diet-B group (p = 0.040). The acute phase protein, serum amyloid A (SAA), was 3.8 times higher in the Diet-B group (p = 0.0038). CONCLUSIONS: IL-10-/- mice fed a TGF-beta 2 containing diet gained more weight, did not develop diarrhea or prolapse, had lower pathological scores, and lower SAAs. These data further support the use of TGF-beta 2 containing enteral diets as one mode of therapy for Crohn's disease.