scholarly journals Inflammatory Profile and Response to Anti-Tumor Necrosis Factor Therapy in Patients with Chronic Pulmonary Sarcoidosis

2011 ◽  
Vol 18 (6) ◽  
pp. 931-939 ◽  
Author(s):  
Matthew J. Loza ◽  
Carrie Brodmerkel ◽  
Roland M. Du Bois ◽  
Marc A. Judson ◽  
Ulrich Costabel ◽  
...  

ABSTRACTSarcoidosis is an inflammatory, granulomatous disease of unknown etiology that most commonly afflicts the lungs. Despite aggressive immunosuppressive therapies, many sarcoidosis patients still chronically present significant symptoms. Infliximab, a therapeutic tumor necrosis factor alpha (TNF-α) monoclonal antibody (MAb), produced a small but significant improvement in forced vital capacity (FVC) in sarcoidosis patients in a double-blind, placebo-controlled, phase II clinical trial. In the current study, serum samples from this clinical trial were assessed to evaluate the underlying hypothesis that treatment with infliximab would reduce systemic inflammation associated with sarcoidosis, correlating with the extent of clinical response. A 92-analyte multiplex panel was used to assess the expression of serum proteins in 134 sarcoidosis patients compared with sera from 50 healthy controls. A strong systemic inflammatory profile was associated with sarcoidosis, with 29 analytes significantly elevated in sarcoidosis (false-discovery rate, <0.05 and >50% higher than controls). The associated analytes included chemokines, neutrophil-associated proteins, acute-phase proteins, and metabolism-associated proteins. This profile was evident despite patients receiving corticosteroids and immunosuppressive therapies. Following infliximab treatment, sarcoidosis patients expressing the highest levels of TNF-α, who had more severe disease, had the greatest improvement in FVC and reduction in serum levels of the inflammatory proteins MIP-1β and TNF-RII. This study supports the need for further exploration of anti-TNF therapy for chronic sarcoidosis patients, particularly for those expressing the highest serum levels of TNF-α.

1995 ◽  
Vol 132 (6) ◽  
pp. 668-672 ◽  
Author(s):  
Ismail Çelik ◽  
Sema Akalin ◽  
Tomris Erbaş

Çelik I, Akalin S, Erbaş T. Serum levels of interleukin 6 and tumor necrosis factor-α in hyperthyroid patients before and after propylthiouracil treatment. Eur J Endocrinol 1995;132:668–72. ISSN 0804–4643 Contrary to the usual inhibitory role of tumor necrosis factor-α (TNF-α) thyroid metabolism, it also has specific stimulatory effects in autoimmune thyroid disorders, including induction of HLA class II antigen-presenting cell—T cell interaction. Despite high intrathyroidal concentrations, various studies were not able to demonstrate high serum levels of TNF-α in patients with Graves' disease. To investigate this discrepancy we determined TNF-α and interleukin 6 (IL-6) levels in 25 hyperthyroid patients who responded to propylthiouracil treatment (16 with Graves' disease and nine with toxic multinodular goiter) and compared them with the levels found in euthyroid patients with simple diffuse goiter (n = 15) and normal healthy controls (n = 15). Median IL-6 levels were high in both Graves' disease and toxic multinodular goiter patients before propylthiouracil treatment (23 and 26.5 pg/ml, respectively). After restoring euthyroidism there was a statistically significant decline to near-normal levels (3 and 10 pg/ml, respectively). On the other hand, median serum TNF-α levels were high only in Graves' disease patients (20 pg/ml) and could not be normalized with antithyroid medication (20 pg/ml) compared to that of controls (5 pg/ml). Tumor necrosis factor-α, but not IL-6, was found to be high in the sera of Graves' disease patients when euthyroid, which may be due to an ongoing antigen–antibody interaction, a feature of autoimmune attack. It remains to be determined whether the degree of TNF-α and/or IL-6 elevation will be a predictor of disease recurrence. Ismail Çelik, Section of Oncology, Dept. of Medicine, Hacettepe University Institute of Oncology, Ankara 06100, Turkey


2010 ◽  
Vol 37 (8) ◽  
pp. 1699-1704 ◽  
Author(s):  
KAOUTHER BEN ABDELGHANI ◽  
DELPHINE GERARD DRAN ◽  
JACQUES-ERIC GOTTENBERG ◽  
JACQUES MOREL ◽  
JEAN SIBILIA ◽  
...  

Objective.To analyze the clinical efficacy of anti-tumor necrosis factor-α (TNF-α) therapy in treatment of synovitis, acne, pustulosis, hyperostosis, osteitis (SAPHO) syndrome, we describe cases of refractory SAPHO syndrome and review cases treated with anti-TNF-α reported in the literature.Methods.We describe 6 cases of patients with SAPHO syndrome treated with anti-TNF-α between 2004 and 2008. Therapeutic response was evaluated according to improvement in pain score, amelioration of disease activity, and improvement in function. The efficacy of treatment was considered to be reduced need for analgesics and/or antiinflammatory therapy.Results.In our series, 4 patients received infliximab, 1 etanercept, and 1 adalimumab. These treatments brought clinical response in 4 patients (66.6%): response was sustained with infliximab in 1 case for 7 months; with adalimumab in another case for 22 months; and with etanercept in 2 cases for 1 and 42 months, respectively. In contrast, 2 other patients showed no response to infliximab. Improvement was initially temporary after infusions 1 and 2, then pain recurred at Week 14. Skin lesions were healed in 3 of 4 cases, but recurred or worsened in 2 cases, after infusion 2 of infliximab. Treatment was generally well tolerated. Paradoxical psoriasis was noted in 2 cases and urticaria in 1.Conclusion.Given our results and those from the literature, TNF-α blockers should be considered in the therapeutic strategy of refractory cases of SAPHO syndrome, despite their effect seeming less impressive than in other spondyloarthropathies.


2015 ◽  
Vol 6 (5) ◽  
pp. 12-16
Author(s):  
Shiv Kumar Yadav ◽  
Qi Jian YI

Objective: To investigate the changes in serum levels of ghrelin, tumor necrosis factor-α and interleukin-6 in Children with Congenital Heart Disease (CHD) at pre and post percutaneous management of the lesions. Material & Methods: We measured the serum levels of ghrelin, tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) by enzyme linked immunosorbent assays (ELISA) in 67 patients with CHD and in 20 control subjects; and compared these markers of inflammatory reaction between groups of pre-closure (37 patients) and at the end of 5 minutes (37 patients), 1 month (22 patients) and 3 month (8 patients) post percutaneous management of the lesions. Results: Our results showed that the patients with CHD had significantly higher serum level of Ghrelin, TNF-α and IL-6 in comparison of the controls but gradually return towards the baseline levels at the end of 3 months post percutaneous management of the lesions. Conclusion: The inflammatory reaction is activated in pre-closure and self-limited post-closure in children with CHD. Percutaneous management could improve the inflammatory process, which is safe and effective in children with CHD.DOI: http://dx.doi.org/10.3126/ajms.v6i5.12129 Asian Journal of Medical Sciences Vol.6(5) 2015 12-16   


1993 ◽  
Vol 48 (3) ◽  
pp. 324-331 ◽  
Author(s):  
Didier Hober ◽  
Bertrand Roblin ◽  
Robert Vergez-Pascal ◽  
Gerard Granic ◽  
Michele Maniez-Montreuil ◽  
...  

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