Cytokine production in patients with recurrent acute tonsillitis: analysis of tonsil samples and blood

Abstract

the aim of this study was to examine t cell function in tonsils of patients with recurrent acute tonsillitis (RAT) or peritonsillar abscess (PTA) by analyzing the cytokine production following T cell receptor (TCR) and co-receptor stimulation with a combination of anti-CD3 and anti-CD28 antibodies. The release of IFN-γ, TNF-α, IL-2, IL-4, IL-6, IL-10 and IL-17A from isolated, stimulated T cells of 27 palatine tonsils (10 RAT, 7 PTA, 10 tonsils without inflammation) was measured via a bead-based flow cytometric analysis. The results were compared with the cytokine release of isolated peripheral T cells in a subset of the same patients (6 PTA, 4 patients without signs of inflammation in the blood). tcR stimulation increased the concentration of released cytokines in tonsil and blood as well as in different forms of inflammation and tissue with no inflammation. Stimulation increased the proinflammatory cytokines TNF-α, IFN-γ, and IL-2 more than the anti-inflammatory cytokines IL-4 and IL-10 in tonsil and blood samples in RAT, PTA, and samples without inflammation. Blood of patients with PTA showed a higher pro-inflammatory cytokine level compared to the samples of patients without inflammation. T cells in tonsils are fully responsive and competent for antigen-induced cytokine production in RAT and PTA. One should be aware that tonsillectomy, if indicated, might remove a functioning immune organ. Tonsillotomy might be an alternative even in adults to maintain immunological function. The palatine tonsils as paired lymphatic organs are located at the beginning of the upper aerodigestive tract and are responsible for immune protection against ingested and inhaled pathogens. In this context, innate and adaptive immune reactions interact, whereby tonsillar T cells located primarily in the extra-follicular spaces, in particular, play a dominant role 1. Cytokines are produced in the context of inflammatory reactions by immunecompetent cells. A distinction is made between genuine pro-inflammatory, e. g. tumor necrosis factor (TNF)-α, interferon (IFN)-γ, interleukin (IL)-2, IL-6, IL17-A, and mostly anti-inflammatory cytokines like IL-4 and IL-10 2-4. Furthermore, depending on the inflammatory scenario, T-cells can differentiate into differently primed states, including Th1, Th2, and Th17. Briefly, Th1 helper cells produce large amounts of IFN-γ, IL-2, and TNF-β, which trigger macrophages and are important for cell-mediated immunity and phagocyte-dependent immune responses. Th2 cells produce IL-4, IL-5, IL-10, and IL-13, which promote antibody production, eosinophil activation, and inhibition of several macrophage functions 5. Th17 cells and their effector cytokines IL-17A, IL-17F, IL-21, and IL-22 mediate host defense mechanisms to a variety of infections, especially of bacterial origin, and are furthermore involved in the pathogenesis of many autoimmune diseases 6. Recurrent acute tonsillitis (RAT) is a common chronic inflammation of the palatine tonsils, which often needs surgical excision 7 .

Prognosis of EBV Infection in Children with Tonsillitis

“…Stimulation increases the pro-inflammatory cytokines TNF-α, IFN-γ and IL-2 more than the anti-inflammatory cytokines IL-4 and IL-10 in tonsil and blood samples in RAT, PTA and noninflammatory samples. The blood of patients with tonsillitis showed higher levels of proinflammatory cytokines compared to the samples of non-inflammatory patients [24]. The present study has also reported this finding.…”

A randomized, open-label, multicentre, comparative study of therapeutic efficacy, preventive potential and tolerability of BNO 1030 extract, containing Althea root, Chamomile flowers, horsetail herb, walnut leaves, yarrow herb, oak bark, dandelion herb in the treatment of acute non-bacterial tonsillitis in children aged 6 to 18 years

“…According to the design, patients with Paradise criteria were not included in our study, i. e. the issue of tonsillectomy was not considered [6,7]. Thus, it was possible to monitor patients for a long time and determine the clinical efficacy of the studied treatment regimens in relation to the recurrence rate of tonsillitis.…”

“…Diagnostic and differential diagnostic criteria for acute tonsillitis were carried out in accordance with the DEGA M recommendations provided in clinical guidelines [2,6]. A clinical diagnosis of AT was established in the presence of such symptoms as sore throat at rest and in swallowing, hyperaemia and swelling with possible plaque on the tonsils, cervical lymphadenitis and fever.…”

“…Present views are based on the fact that tonsils are constantly in a state of "minimal" inflammatory process without tissue alteration when fulfilling their main taskformation of immunity. This is their physiological norm and is histopathologically determined in anamnestically healthy patients [5,6]. Given these views, the term "chronic tonsillitis" should not be used at present, since an erroneous opinion is being created about the absence of tonsillitis in clinically healthy patients, especially in children.…”

“…Unjustified prescription of antibiotics is one of the main causes of the global problem of antibiotic resistance, since inadequate antibiotic therapy is prescribed in more than 50% of cases worldwide according to WHO data [11,12]. However, it is indisputable that qualitative randomized controlled trials are required in order to clarify the possibilities of nonsurgical treatment in patients with RT without indications for tonsillectomy (Paradise criteria) [2,6].…”