Dual role of anti-TNF therapy: Enhancement of TCR-mediated T cell activation in peripheral blood and inhibition of inflammation in target tissues

Bosè, Francesca; Raeli, Lorenzo; Garutti, C.; Frigerio, E.; Cozzi, Alessandra; Crimi, Marco; Caprioli, Flavio; Scavelli, Rossana; Gf, Altomare; Geginat, Jens; Abrignani, Sergio; Reali, Eva

doi:10.1016/j.clim.2011.01.015

Cited by 44 publications

(34 citation statements)

References 31 publications

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“…It is unknown what impact TNF-a inhibitor therapy has on IL-10 expression. One study in adult patients with inflammatory bowel disease (IBD) or psoriasis similarly described increased IL-10 levels after treatment with either etanercept, adalimumab or infliximab, despite clinical improvement [21]. We theorize that the higher levels of IL-10 in our anti-TNF subjects may have been an anti-inflammatory response to the higher disease activity in our anti-TNF subjects versus non-TNF subjects.…”

Section: Discussionmentioning

confidence: 71%

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The impact of disease activity and tumour necrosis factor-α inhibitor therapy on cytokine levels in juvenile idiopathic arthritis

Walters

Pan

Lehman

et al. 2016

Clinical and Experimental Immunology

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Summary The aim of this study was to evaluate prospectively cytokine levels and disease activity in juvenile idiopathic arthritis (JIA) patients treated with and without tumour necrosis factor (TNF)-α inhibitors. TNF-α inhibitor-naive JIA subjects were followed prospectively for 6 months. Cytokine levels of TNF-α, interleukin (IL)−1β, IL-6, IL-8, IL-10 and IL-17 were measured at baseline for JIA subjects and healthy controls (HCs). Cytokine levels were then measured at four time-points after initiation of TNF-α inhibition for anti-TNF-α-treated (anti-TNF) JIA subjects, and at two subsequent time-points for other JIA (non-TNF) subjects. JIA disease activity by Childhood Health Assessment Questionnaire (CHAQ) disability index/pain score and physician joint count/global assessment was recorded. Sixteen anti-TNF, 31 non-TNF and 16 HCs were analysed. Among JIA subjects, those with higher baseline disease activity (subsequent anti-TNFs) had higher baseline TNF-α, IL-6 and IL-8 than those with lower disease activity (non-TNFs) (P < 0·05). TNF-α and IL-10 increased, and IL-6 and IL-8 no longer remained significantly higher after TNF-α inhibitor initiation in anti-TNF subjects. Subgroup analysis of etanercept versus adalimumab-treated subjects showed that TNF-α and IL-17 increased significantly in etanercept but not adalimumab-treated subjects, despite clinical improvement in both groups of subjects. JIA subjects with increased disease activity at baseline had higher serum proinflammatory cytokines. TNF-α inhibition resulted in suppression of IL-6 and IL-8 in parallel with clinical improvement in all anti-TNF-treated subjects, but was also associated with elevated TNF-α and IL-17 in etanercept-treated subjects.

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Section: Discussionmentioning

confidence: 71%

“…No past studies have evaluated IL-17 levels prospectively in JIA patients. One adult study described increased IL-17 levels in patients with psoriasis and IBD treated with etanercept, adalimumab or infliximab [21]. This occurred similarly despite clinical improvement in treated subjects.…”

Section: Discussionmentioning

confidence: 94%

The impact of disease activity and tumour necrosis factor-α inhibitor therapy on cytokine levels in juvenile idiopathic arthritis

Walters

Pan

Lehman

et al. 2016

Clinical and Experimental Immunology

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“…In vivo administration of anti-TNF-␣ to patients results in increase of IL-17 and IFN-␥ secretion by in vitro anti-CD3-stimulated PBMCs, and half of the IBD patients are reported to be refractory to anti-TNF-␣ therapy. 50 In conclusion, the results of the present study demonstrate that human basophils accumulate in inflamed IBD tissues and amplify inflammatory memory Th17 cell responses. This suggests that basophils represent previously unknown innate players that, together with eosinophils and neutrophils, are recruited to sites of inflammatory reaction to control the exacerbation of inflammatory responses.…”

Section: Discussionmentioning

confidence: 73%

Human basophils interact with memory T cells to augment Th17 responses

Wakahara

Baba

Van

et al. 2012

Blood

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Basophils are a rare population of granulocytes that have long been associated with IgE-mediated and Th2-associated allergic diseases. However, the role of basophils in Th17 and/or Th1 diseases has not been reported. In the present study, we report that basophils can be detected in the mucosa of Th17-associated lung and inflammatory bowel disease and accumulate in inflamed colons containing large quantities of IL-33. We also demonstrate that circulating basophils increased memory Th17 responses. Accordingly, IL-3-or IL-33-activated basophils amplified IL-17 release in effector memory T cells (T EM ), central memory T cells (T CM) IntroductionBasophils are the least abundant of the granulocyte population, accounting for only 0.5%-1% of circulating leukocytes, and, together with eosinophils and mast cells (MCs), have long been associated with allergic diseases and helminth infections. [1][2][3][4] Like MCs, basophils express the tetrameric form of the high-affinity receptor for IgE (Fc⑀RI) and are a major source of histamine, which is stored in their cytoplasmic basophilic granules. Basophils and MCs belong to distinct cell lineages and are biologically very different. 5 Basophils are short-lived circulating cells (estimated half-life of 2 days) that differentiate and mature in the BM, whereas MCs are long-lived, tissue-resident cells that differentiate in peripheral tissues from locally recruited circulating CD34 ϩ precursors released from the BM. MCs are easily detectable at the interface of the organism with the external world; in contrast, basophils are rarely found in normal tissues, but can be detected by immunohistochemistry in inflamed tissues of patients with asthma, allergic rhinitis, and various allergic skin diseases. 1,6,7 However, the presence of basophils in the mucosa of patients with inflammatory diseases that are independent of IgE has not been reported.The CD4 T cells play a key role in orchestrating the pathologic immune reaction of chronic inflammatory disorders. It is now known that Th17 effectors play a crucial role in pulmonary cystic fibrosis (CF). 8 Similarly, Th17 and Th1 cells are involved in mucosa-associated chronic disorders such as inflammatory bowel disease (IBD), which include Crohn's disease (CD) and ulcerative colitis (UC). 9-11 Specifically, CD is a chronic and relapsing T cell-driven inflammatory disease of the entire gastrointestinal tract. CD4 effector T cells are generated in draining lymph nodes and recruited into the intestinal tissues, where they contribute to the inflammatory process and tissue destruction. 9 Once initiated, inflammation is first characterized by the expression of proinflammatory cytokines involved in innate immunity (ie, IL-12, TNF-␣, and IL-23), followed by those involved in adaptive immunity (ie, . 9,12 APC-derived IL-1␤, together with IL-6, promotes the development of human Th17 cells in vitro. 13 IL-23 promotes the expansion of memory Th17 cells. 14 In mice, IL-23 drives pathogenic Th17/Th1 cells. 15 Double IL-17-and IFN-␥-producing CD4 T cells ar...

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“…The recent paper by Bosè et al [23] reported however conflicting results, showing that anti-TNF therapy exerts a dual role by enhancing Th1/Th17 cell activation in peripheral blood whilst inhibiting T cell responses, cytokine release and early inflammatory genes in the skin.…”

Section: Introductionmentioning

confidence: 99%

Th1, Th2, Th17 and Regulatory T Cell Pattern in Psoriatic Patients: Modulation of Cytokines and Gene Targets Induced by Etanercept Treatment and Correlation with Clinical Response

Quaglino¹,

Bergallo

Ponti³

et al. 2011

Dermatology

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Background: Psoriasis is sustained by pro-inflammatory CD4+ T helper cells mainly belonging to the Th1, Th17 and Th22 lineage. Objective: To identify whether treatment with the anti-tumour-necrosis-factor antagonist etanercept is able to induce significant modulations in transcription factor and cytokine mRNA gene expressions related to the different T cell immune response polarization (Th1, Th2, Th17 and regulatory T cells, T_reg) and to correlate them with clinical response. Methods: The study population included 19 psoriasis patients treated with etanercept and 19 healthy subjects. Blood samples were collected at baseline and every 4 weeks during treatment. Taqman quantitative real-time polymerase chain reaction was applied to analyse the expression of: Stat-4, T-bet, IL-12p35 and IFN-γ (Th1-related); GATA-3, IL-4 (Th2-related); Stat-3, RORγt, IL-23p19 (Th17-related); Foxp3, IL-2 (T_reg-related). Flow cytometry was applied to analyse CD4+CD25+^brightFoxp3+ cells in peripheral blood. Results: Upregulation of Th1 and Th17 and downregulation of T_reg subsets was found at baseline. The response to etanercept could be associated with a significant reversal of the Th1/Th17 activation, and a concomitant upregulation of Th2 and T_reg subsets. Conclusion: Our data may contribute to a better understanding of the mechanisms underlying the achievement of clinical response in psoriasis and could be helpful for the identification of early predictive markers of response.

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Dual role of anti-TNF therapy: Enhancement of TCR-mediated T cell activation in peripheral blood and inhibition of inflammation in target tissues

Cited by 44 publications

References 31 publications

The impact of disease activity and tumour necrosis factor-α inhibitor therapy on cytokine levels in juvenile idiopathic arthritis

The impact of disease activity and tumour necrosis factor-α inhibitor therapy on cytokine levels in juvenile idiopathic arthritis

Human basophils interact with memory T cells to augment Th17 responses

Th1, Th2, Th17 and Regulatory T Cell Pattern in Psoriatic Patients: Modulation of Cytokines and Gene Targets Induced by Etanercept Treatment and Correlation with Clinical Response

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