scholarly journals 1356. A Randomized Controlled Trial of Prednisolone vs. TNF-α inhibitor Infliximab in the Management of Type 1 Lepra Reaction in Leprosy Patients

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S491-S491
Author(s):  
Ajay Chopra ◽  
Debdeep Mitra
Keyword(s):  
Adverse Events ◽  
Tumor Necrosis ◽  
Necrosis Factor Alpha ◽  
Tnf Α ◽  
Factor Alpha ◽  
Randomized Control ◽  
Biologic Drug ◽  
Necrosis Factor

Abstract Background Leprosy is a chronic granulomatous infectious disease caused by Mycobacterium leprae. Type 1 lepra reactions (T1R) are an acute inflammatory response during the chronic course of the disease. If it is not treated promptly with immune suppression, it can lead to a permanent disability affecting hands, feet and eyes. tumor necrosis factor-alpha (TNF-a) which is produced mainly by inflammatory T cells is up-regulated in patients of Type I Lepra reaction. Conventionally oral corticosteroids steroids have been the mainstay in the management of Type 1 Lepra reactions. This novel biologic drug is a targeted therapy which blocks the offending interleukin molecule without any serious adverse effects. We report the results of this randomized control study wherein an immuno-modulator biologic molecule has been safely used to treat an inflammatory reaction in a chronic infectious disease. Outcomes were measured using recurrence rate, a clinical severity score, quality of life and adverse events. Methods 62 patients with new Type 1 Lepra reactions were randomized to receive Infliximab (a chimeric monoclonal antibody biologic drug that works against tumor necrosis factor-alpha (TNF-α) or Prednisolone for 20 weeks. TNF-α levels were correlated before and after the intervention. Results Recovery rates in skin signs were similar in both groups (91% vs. 86%). Improvements in nerve function both, new and old, sensory (68% vs. 49%) and motor (72% vs. 77%) loss were higher (but not significantly so) in the patients on Infliximab. Recurrences rates of lepra reaction (24%) were high in both groups, and recurrences occurred significantly earlier (8 weeks) in patients on Infliximab, who needed 10% more additional prednisolone. Serious major and minor adverse events rates were much lesser with Infliximab as compared with Prednisolone alone. Both groups had a significant improvement in their quality of life after the study, measured by the short-form survey SF-36. Conclusion This is the first double-blind randomized control trial assessing Infliximab, in the management of lepra reaction. It could be a safe alternative second-line drug for patients with leprosy reactions who are not improving with prednisolone or are experiencing adverse events related to prednisolone. Disclosures All authors: No reported disclosures.

scholarly journals Role of Adiponectin and Tumor Necrosis Factor-Alpha in the Pathogenesis and Evolution of Type 1 Diabetes Mellitus in Children and Adolescents

Diagnostics ◽  
2020 ◽  
Vol 10 (11) ◽  
pp. 945
Author(s):  
Csilla Enikő Szabo ◽  
Oana Iulia Man ◽  
Alexandru Istrate ◽  
Eva Kiss ◽  
Andreea Catana ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Tumor Necrosis ◽  
Diabetic Patients ◽  
Necrosis Factor Alpha ◽  
Tnf Α ◽  
Risk Patients ◽  
Factor Alpha ◽  
Necrosis Factor

Type 1 diabetes mellitus (T1DM) is a complex condition caused by the destruction of pancreatic beta cells by autoimmune mechanisms. As a result, insulin deficiency and subsequent hyperglycemia occur. The aim of the present study is to investigate the role of adiponectin and tumor necrosis factor alpha (TNF-α) in the development of T1DM. The study is designed as an observational case-control study, involving 52 diabetic patients and 66 controls. Z scores for Body Mass Index (BMI), weight, height, and adiponectin and TNF-α serum levels were assessed in both groups. The T1DM group had significantly higher TNF-α levels and a significantly higher proportion of high-risk patients for inflammation based on TNF-α values as compared to the control group, while both groups had statistically similar adiponectin levels and a similar proportion of high/medium-risk patients based on adiponectin values. TNF-α plays a significant role in the pathogenesis and evolution of T1DM and it may represent an additional marker of disease progression, as well as a potential target of immunotherapeutic strategies. In the present study, no statistically significant differences were recorded in adiponectin levels neither in diabetic patients and controls, nor in high/medium severity risk diabetic patients.

scholarly journals Neutralization of Tumor Necrosis Factor Alpha Suppresses Antigen-Specific Type 1 Cytokine Responses and Reverses the Inhibition of Mycobacterial Survival in Cocultures of Immune Guinea Pig T Lymphocytes and Infected Macrophages

2005 ◽  
Vol 73 (12) ◽  
pp. 8437-8441 ◽  
Author(s):  
Hyosun Cho ◽  
David N. McMurray
Keyword(s):  
Tumor Necrosis Factor ◽  
Tumor Necrosis Factor Alpha ◽  
Tumor Necrosis ◽  
T Cell Response ◽  
Interleukin 12 ◽  
Necrosis Factor Alpha ◽  
Tnf Α ◽  
Factor Alpha ◽  
Necrosis Factor

ABSTRACT Neutralization of tumor necrosis factor alpha (TNF-α) significantly down-regulated antigen-induced lymphoproliferation and the expression of interleukin-12 p40 and gamma interferon mRNA and enhanced the viability of intracellular attenuated and virulent mycobacteria in cocultures of immune T cells and macrophages obtained from Mycobacterium bovis BCG-vaccinated guinea pigs. This suggests the crucial role of TNF-α in the activation of a type 1 T-cell response against Mycobacterium tuberculosis infection.

scholarly journals Modulation of Type 1 Diabetes Susceptibility by Tumor Necrosis Factor Alpha −308 G/A and Lymphotoxin Alpha +249 A/G Haplotypes and Lack of Linkage Disequilibrium with Predisposing DQB1-DRB1 Haplotypes in Bahraini Patients

2007 ◽  
Vol 15 (2) ◽  
pp. 379-381 ◽  
Author(s):  
Mouna Stayoussef ◽  
Fayza A. Al-Jenaidi ◽  
Abduljabbar Al-Abbasi ◽  
Khadija Al-Ola ◽  
Haya Khayyat ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Linkage Disequilibrium ◽  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Necrosis Factor Alpha ◽  
Tnf Α ◽  
Factor Alpha ◽  
Lymphotoxin Alpha ◽  
Necrosis Factor

ABSTRACT Tumor necrosis factor alpha (TNF-α) −308 G/A and lymphotoxin alpha (LTα) +249 A/G single-nucleotide polymorphisms were investigated in 228 type 1 diabetes mellitus (T1DM) patients and 240 controls. Only LTα +249G allele and +249G/+249G genotype frequencies were higher among patients, and no linkage disequilibrium was found between TNF-α/LTα alleles and susceptible/protective DRB1-DQB1 haplotypes. TNF-α/LTα T1DM-susceptible (−308G/+249G) and protective (−308G/+249A) haplotypes were identified.

scholarly journals Elevated Levels of Tumor Necrosis Factor Alpha (TNF-α) in Human Immunodeficiency Virus Type 1-Transgenic Mice: Prevention of Death by Antibody to TNF-α

2002 ◽  
Vol 76 (22) ◽  
pp. 11710-11714 ◽  
Author(s):  
Swapan K. De ◽  
Krishnakumar Devadas ◽  
Abner Louis Notkins
Keyword(s):  
Human Immunodeficiency Virus ◽  
Transgenic Mice ◽  
Tumor Necrosis ◽  
Necrosis Factor Alpha ◽  
Tnf Α ◽  
Immunodeficiency Virus ◽  
Factor Alpha ◽  
Hiv 1 ◽  
Necrosis Factor

ABSTRACT Homozygous human immunodeficiency virus type 1 (HIV-1)-transgenic mice (Tg26) appear normal at birth but die within 3 to 4 weeks. The skin of these animals shows diffuse scaling and high-level expression of both HIV-1 mRNA and gp120. Previous experiments showed that treatment with human chorionic gonadatropin (hCG) prevented death and the expression of HIV-1 mRNA and gp120. The present experiments were initiated to study the role of tumor necrosis factor alpha (TNF-α) in HIV-1-induced pathology. Examination of the sera of Tg26 mice revealed a 50-fold increase in TNF-α levels compared to those in nontransgenic mice. Treatment with antibody to TNF-α prevented death, resulted in near normal growth, and produced a marked decrease in skin lesions and a profound reduction in the expression of HIV-1 mRNA and gp120. Both TNF-α antibody and hCG reduced TNF-α levels in sera by approximately 75%. We conclude that TNF-α contributes in a major way to HIV-1-induced pathology in transgenic mice and that both hCG and antibody to TNF-α prevent the development of pathology by suppressing the level of TNF-α.

scholarly journals Human T-Cell Lymphotropic Virus Type 1-Infected T Lymphocytes Impair Catabolism and Uptake of Glutamate by Astrocytes via Tax-1 and Tumor Necrosis Factor Alpha

2000 ◽  
Vol 74 (14) ◽  
pp. 6433-6441 ◽  
Author(s):  
Raphaël Szymocha ◽  
Hideo Akaoka ◽  
Magali Dutuit ◽  
Christophe Malcus ◽  
Marianne Didier-Bazes ◽  
...  
Keyword(s):  
T Cells ◽  
T Lymphocytes ◽  
Tumor Necrosis ◽  
Necrosis Factor Alpha ◽  
Human T Cell ◽  
Tnf Α ◽  
Factor Alpha ◽  
Transient Contact ◽  
Necrosis Factor

ABSTRACT Human T-cell lymphotropic virus type 1 (HTLV-1) is the causative agent of a chronic progressive myelopathy called tropical spastic paraparesis/HTLV-1-associated myelopathy (TSP/HAM). In this disease, lesions of the central nervous system (CNS) are associated with perivascular infiltration by lymphocytes. We and others have hypothesized that these T lymphocytes infiltrating the CNS may play a prominent role in TSP/HAM. Here, we show that transient contact of human or rat astrocytes with T lymphocytes chronically infected by HTLV-1 impairs some of the major functions of brain astrocytes. Uptake of extracellular glutamate by astrocytes was significantly decreased after transient contact with infected T cells, while the expression of the glial transporters GLAST and GLT-1 was decreased. In two-compartment cultures avoiding direct cell-to-cell contact, similar results were obtained, suggesting possible involvement of soluble factors, such as cytokines and the viral protein Tax-1. Recombinant Tax-1 and tumor necrosis factor alpha (TNF-α) decreased glutamate uptake by astrocytes. Tax-1 probably acts by inducing TNF-α, as the effect of Tax-1 was abolished by anti-TNF-α antibody. The expression of glutamate-catabolizing enzymes in astrocytes was increased for glutamine synthetase and decreased for glutamate dehydrogenase, the magnitudes of these effects being correlated with the level of Tax-1 transcripts. In conclusion, Tax-1 and cytokines produced by HTLV-1-infected T cells impair the ability of astrocytes to manage the steady-state level of glutamate, which in turn may affect neuronal and oligodendrocytic functions and survival.

scholarly journals Tumor Necrosis Factor Alpha and Gamma Interferon, but Not Hemorrhage or Pathogen Burden, Dictate Levels of Protective Fibrin Deposition during Infection

2006 ◽  
Vol 74 (2) ◽  
pp. 1181-1188 ◽  
Author(s):  
Isis K. Mullarky ◽  
Frank M. Szaba ◽  
Kiera N. Berggren ◽  
Lawrence W. Kummer ◽  
Lindsey B. Wilhelm ◽  
...  
Keyword(s):  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Fibrin Deposition ◽  
Necrosis Factor Alpha ◽  
Tnf Α ◽  
Factor Alpha ◽  
Ifn Γ ◽  
Pathogen Burden ◽  
Necrosis Factor

ABSTRACT While coagulation often causes pathology during infectious disease, we recently demonstrated that fibrin, a product of the coagulation pathway, performs a critical protective function during acute toxoplasmosis (L. L. Johnson, K. N. Berggren, F. M. Szaba, W. Chen, and S. T. Smiley, J. Exp. Med. 197:801-806, 2003). Here, we investigate the mechanisms regulating the formation of this protective fibrin. Through comparisons of Toxoplasma-infected wild-type and cytokine-deficient mice we dissociate, for the first time, the relative fibrin-regulating capacities of pathogen products, host cytokines, and infection-stimulated hemorrhage. Remarkably, neither the pathogen burden nor hemorrhage is a primary regulator of fibrin levels. Rather, two type 1 cytokines exert dominant and counterregulatory roles: tumor necrosis factor alpha (TNF-α), acting via the type 1 TNF-α receptor, promotes fibrin deposition, while gamma interferon (IFN-γ), acting via STAT1 and IFN-γ receptors expressed on radioresistant cells, suppresses fibrin deposition. These findings have important clinical implications, as they establish that cytokines known to regulate pathological coagulation also dictate levels of protective fibrin deposition. We present a novel model depicting mechanisms by which the immune system can destroy infected tissue while independently restraining hemorrhage and promoting tissue repair through the deliberate deposition of protective fibrin.

scholarly journals Uniocular Anterior Chamber Inoculation of a Tumor Necrosis Factor Alpha-Expressing Recombinant of Herpes Simplex Virus Type 1 Results in More Rapid Destruction and Increased Viral Replication in the Retina of the Uninoculated Eye

2008 ◽  
Vol 82 (10) ◽  
pp. 5068-5078 ◽  
Author(s):  
Mark A. Fields ◽  
Mei Zheng ◽  
Pam Wall ◽  
Scott Oberg ◽  
Sally S. Atherton
Keyword(s):  
Herpes Simplex ◽  
Tumor Necrosis ◽  
Inflammatory Cells ◽  
Virus Spread ◽  
Necrosis Factor Alpha ◽  
Tnf Α ◽  
Factor Alpha ◽  
Simplex Virus ◽  
Necrosis Factor

ABSTRACT Tumor necrosis factor alpha (TNF-α) has been shown to have a protective role in the eyes and brains of herpes simplex virus type 1 (HSV-1)-infected mice. To determine whether overexpression of TNF-α affected the course of virus infection following uniocular anterior chamber inoculation, a recombinant of HSV-1 that produces TNF-α constitutively (KOSTNF) was constructed. BALB/c mice were injected with the TNF-α recombinant, a recombinant containing the pCI plasmid, a recombinant rescue virus, or the parental virus. Flow cytometry and immunohistochemistry were used to identify virus-infected cells and to determine the numbers and types of infiltrating inflammatory cells in the uninjected eyes. Virus titers were determined by plaque assay. There were no differences among the groups in virus titers or the route and timing of virus spread in the injected eyes or in the suprachiasmatic nuclei. However, in the uninjected eyes of KOSTNF-infected mice, TNF-α expression was increased and there were more viral antigen-positive cells and immune inflammatory cells. There was earlier microscopic evidence of retinal infection and destruction in these mice, and the titers of virus in the uninjected eyes were significantly increased in KOSTNF-infected mice on day 7 postinfection compared with those of KOSpCI-, KOS6βrescue-, or KOS6β-infected mice. The results suggest that instead of moderating infection and reducing virus spread, overexpression of TNF-α has deleterious effects due to increased inflammation and virus infection that result in earlier destruction of the retina of the uninoculated eye.

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