There is no available consensus in general, due to the lack of large patient registries and randomized controlled trials, yet this review aims to sketch the contemporary strategies promised to counteract myocardial inflammation and to minimize its impact on the myocardium. bacteria, toxic substances, and autoantigens are other frequent etiologies [2, 3]. Myocarditis may spontaneously resolve without clinical footprints or remain active, instigating a chronic inflammatory course that culminates IKK 16 hydrochloride into inflammatory cardiomyopathy (Infl-CM), characterized by left ventricular (LV) dysfunction and heart failure or arrhythmias [1C4]. Cardiotropic microbes and cardiotoxins induce acute myocarditis via direct activation of the host immune system or via induction of myocyte necrosis and exposure of normally hidden antigens [2, 4]. Although in the acute phase, cardiac inflammation can be detected by cardiac magnetic resonance imaging, endomyocardial biopsy (EMB) analysis is the only diagnostic tool capable of identifying the underlying etiology of cardiac inflammation, allowing quantification of immune cell subtypes and microbial nucleic acid [2, 5C7]. The associated inflammatory processes are diverse and complex, including microbial or nonmicrobial inducers (e.g., alarmins, extracellular matrix fragments, and self-proteins), which activate immune sensors (e.g., inflammasomes, Toll-like receptors) and several kinds of mediators including cytokines, chemokines (e.g., CC-chemokine ligand (CCL)2 and CCL7), eicosanoids (e.g., prostaglandins), biogenic amines (e.g., histamine), and bioactive peptides (e.g., bradykinin) [8]. Being the major peripheral lymphatic reservoir of monocytes and filter of viruses, the spleen plays a major role in the development of Infl-CM. Monocytes from the spleen home to the heart (cardiosplenic axis), where they next contribute to tissue injury and cardiac remodeling IKK 16 hydrochloride [9C13]. Immunosuppressant agents like lympholytic, anti-proliferative agents and proliferation signal inhibitors are seen as potential therapies for myocardial inflammation, frequently indicated as off-label treatments or used in the context of clinical studies. For the moment, most clinical studies in this arena are investigator-initiated, and there is a lack of sufficient information concerning the clinical value of individual immunosuppressive agents. Etiology-based treatment protocols are needed for which EMB analysis subclassifies the patients to different strata [8]. There is no available consensus in general, due to the lack of large patient registries and randomized controlled trials, yet this review aims to sketch the contemporary strategies promised to counteract myocardial inflammation and to minimize its impact on the myocardium. The order of available strategies is built on the degree of clinical and experimental FABP7 evidence, starting with (I) global immunosuppressive strategies antagonizing cellular and humoral immunity, followed by strategies, which (II) systemically modulate the immune response, (III) antagonize key inflammatory components, (IV) reduce myocardial wall stress via mechanical unloading, and (V) decrease mimic peptides-driven anti-cardiac autoimmunity via antibiotic therapy (Table ?(Table11). Table 1 Overview of available immune-related strategies suggested for the treatment of inflammatory cardiomyopathy mimic peptides. This might also be of relevance in the context of virus-induced or virus-associated Infl-CM and needs further investigation. Discussion Systemic immunosuppression is the most potent strategy to defeat myocardial inflammation. Theoretically, any combination of immunosuppressant agents that harbor no hazardous interactions can be considered for Infl-CM treatment. The choice of whether to administer immunosuppressive agents should be IKK 16 hydrochloride seen as personalized practice, based on the whole clinical picture including other comorbidities, type of immune infiltrates, and microbes detected in the myocardium. Every regimen has to be weighed against the risk of infection, including reactivation of latent cardiac microbial infections, outburst of present cardiac virulent infections, and novel infections. Corticosteroids are found almost indispensable in every immunosuppressive combination, attributed to their chief anti-inflammatory activity. The dose of steroids required to produce an anti-inflammatory action is lower, compared with the immunosuppressive dose [16, 147]. Combining prednisolone with potent immunosuppressant agents allows steroid dose reduction while preserving the anti-inflammatory mechanism. This approach shields prone patients like diabetics against steroid adverse effects. Clinical experience with the individual immunosuppressive agents is a major factor in the selection of the regimen by the treating physicians, which favors corticosteroids to IKK 16 hydrochloride a large extend. An immunosuppressive regimen should be initiated at low dose with up titration and may be stepped up to include different classes of immunosuppressant agents (Fig. ?(Fig.1),1), while through blood levels and common side effects need to be real-time monitored. The treatment protocols need to be shaped and synchronously refined based on the treatment associated benefits and risks aiming to achieve the best therapeutic outcome. More specific strategies meant to block specific myocarditis-related inflammatory mechanisms are currently under investigation yet barely used clinically against myocarditis due to the very limited availability of safety and efficacy data. Colchicine, the relatively cheap old-timer drug, can be an alternative.
