T-lymphocytes and cytokines in sarcoidosis

Agostini, Carlo; Meneghin, Alessia; Semenzato, Gianpietro

doi:10.1097/00063198-200209000-00016

Cited by 80 publications

(63 citation statements)

References 27 publications

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“…36 Another important fi nding is the increased levels of proinfl ammatory cytokines such as tumor necrosis factor-α (TNFα) in sarcoidosis. 37,38 TNFα exerts its effect by binding to specifi c cell surface receptors such as membrane TNF receptor (mTNFR)-1 and mTNFR-2, and can be blocked by soluble TNF receptor (sTNFR)-1 and sTNFR-2. 39 Because of these properties, in the past several years, both TNFα monoclonal antibody and soluble TNF receptor have been investigated for the treatment of sarcoidosis, and ocular involvement as well.…”

Section: Lacrimal Gland Infl Ammationmentioning

confidence: 99%

The role of inflammation and antiinflammation therapies in keratoconjunctivitis sicca

Gümüş

Cavanagh

2008

OPTH

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Purpose: To review and integrate recent advances in identifying the role of infl ammation in the pathogenesis of dry eye conditions and the biological rationale and practical clinical aspects of newer, antiinfl ammatory theories. Methods: A comprehensive literature survey. Results and conclusion: Keratoconjunctivitis Sicca (KCS) is a multifactorial and complex disorder in which ocular surface infl ammations play a central role. Identifi cation of specifi c CD4-T-Cell pathways and the recent recognition of targeting of alpha-fodrin suggest a case for novel new therapeutic aspects such as anti-CD4 monoclonal antibodies, systemic linoleic and gamma-linolenic acids, and omega-6 essential fatty acids. Replacement of tear volume with nonpreserved wetting agents and standard typical antiinfl ammatory corticosteroid and/or cyclosporine A continues to be central current conventional therapy for KCS. Keywords: dry eye, keratoconjunctivitis sicca, antiinfl ammatory therapy Dry eye disease or keratoconjunctivitis sicca (KCS) is a common disorder which refers to a spectrum of ocular surface diseases with multiple etiologies.1 KCS is associated with symptoms of ocular discomfort such as burning, sense of dryness, foreign body sensation, ocular pain, and is sometimes associated with photophobia, blurred vision, visual fatigue, and sight-threatening corneal complications in severe cases. 2,3Epidemiologic studies have stated that more than 6% of the population complains of dry eye symptoms, and this ratio increases to 15% over the age of 65. [4][5][6] Most of the studies have also found an increasing prevalence with aging and greater prevalence among women due to the hormonal status. 4,6,7 Pathogenesis of KCS has not been completely clarified. Even though KCS has been thought of classically and basically as a condition of tear deficiency, whether caused by decreased lacrimation or excessive evaporation, it is a complex disorder. Many clinicopathological entities involving tear film, lacrimal glands, eyelids, and a wide spectrum of ocular surface cells, including epithelial, inflammatory, immune, and goblet cells may play a role in its pathogenesis. 2,8Over the past years, as a result of numerous studies, new concepts of pathogenesis have shown that KCS seems to be caused by infl ammation mediated by T-cell lymphocytes. [9][10][11] This fi nding has also been augmented by the studies investigating the role of antiinfl ammatory therapies. For instance, the treatment of KCS gained a new dimension with the approval of topical 0.05% cyclosporine A (Restasis) (Allergan, Inc., package insert for Restasis) by the US Food and Drug Administration. Consequently, because of the increasing importance of the role of infl ammation and the use of cyclosporine eye drops, the goal of this review article is to provide the readers with an overview of Clinical Ophthalmology downloaded from https://www.dovepress.com/ by 35.167.132.9 on 10-May-2018 For personal use only.Powered by TCPDF (www.tcpdf.org)

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Section: Lacrimal Gland Infl Ammationmentioning

confidence: 99%

The role of inflammation and antiinflammation therapies in keratoconjunctivitis sicca

Gümüş

Cavanagh

2008

OPTH

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“…A number of considerations are currently fundamental to the understanding of sarcoidosis: 1) the disease is defined by the presence of granulomas, rarely with caseation but often with fibrinoid necrosis [3]; 2) sites of granulomatous inflammation contain variable numbers of activated T-cells and cells from the monocyte/macrophage lineage [4,5]; 3) these T-cells, macrophages and other local tissue cells express many pro-inflammatory cytokines and chemokines that have been shown experimentally to be critical in cell-mediated immune responses and granuloma formation, with a role for transforming growth factor-b in spontaneous resolution of granulomas [6][7][8]; 4) sarcoidosis is associated with a T-helper cell type 1 immune response, at least in the initial years of disease [9]; 5) T-cell expansion is oligoclonal, consistent with an antigen-driven immune response [10,11]; 6) multiple aetiological agents have been suggested to initiate this response, e.g. exposure to specific microorganisms such as Propionibacterium acnes, but no causation has been established to date [12]; 7) recently, evidence has been found for a loss of immunoregulation by CD1d-restricted natural killer T-cells and a genetically determined dysfunction of a putative co-stimulatory molecule (butyrophilin-like protein 2) [13,14]; and 8) Lö fgren's syndrome, the subset of sarcoidosis with the best prognosis, is associated with the formation of circulating immune complexes and specific human leukocyte antigen and nonhuman leukocyte antigen genotypes essentially 100% of the time [15][16][17].…”

Section: Basic Considerationsmentioning

confidence: 99%

Corticosteroid treatment in sarcoidosis

Grutters

Bosch²

2006

Eur Respir J

168

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At present there is no curative treatment for sarcoidosis. Immunosuppressive and/or immunomodulatory drugs can, however, be used for controlling the disease.Corticosteroids remain the mainstay of therapy. They function by suppressing the proinflammatory cytokines and chemokines that are involved in cell-mediated immune responses and granuloma formation. Only in a select group of patients is it justifiable to use these drugs, after careful evaluation of the pros and cons. Importantly, disease severity, e.g. threatened organ functions, and not disease activity itself should be the deciding factor in this process.In the case of parenchymal involvement, there is substantial evidence that corticosteroids can improve respiratory symptoms and chest radiography and lung function parameters over 6-24 months. Other generally acknowledged (empirical) criteria for systemic treatment include neurological, cardiac and sight-threatening ocular involvement and hypercalcaemia. Remarkably, despite .50 yrs of use, there is no proof of long-term (survival) benefit from corticosteroid treatment. In addition, there are still no data regarding the optimal dose and duration of corticosteroid or other immunosuppressive therapy.One of the weightiest questions remaining is whether or not these drugs can prevent scarring in patients with a fibrogenic phenotype. As new agents, including infliximab and thalidomide, enter the stage and new diagnostic tools are now available, there is clearly a momentum to design multicentric randomised controlled trials with long enough follow-up (.5 yrs) to answer this pivotal question.

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“…In pulmonary sarcoidosis, the T4:T8 ratio of bronchoalveolar fluid mirrors treatment response. 2 Nonimprovement of the T4:T8 ratio with cyclosporine proved lack of benefit of that drug in pulmonary sarcoid. 7 In our patient, post-treatment T4:T8 ratio reflected his clinical picture with considerable improvement.…”

Section: Com/scmentioning

confidence: 99%

“…1 In contrast, pulmonary sarcoidosis has characteristic immunocytologic changes in alveolar fluid. 2 Small studies suggest an elevated ratio of CSF CD4:CD8 þ (T helper:T suppressor or T4:T8) lymphocytes in neurosarcoidosis. 3 We present a patient with sarcoid myelopathy whose clinical and radiographic diagnosis and treatment response correlated with the CSF immune profile.…”

Section: Introductionmentioning

confidence: 99%