Editorial [Hot Topic: Trends in Inflammation - Leads in Immunopharmacology (Guest Editor: Ekaterini Tiligada)]

Inflammatory reactions have attracted wide interest lately, as a consequence of their contribution to abnormalities additional to the long-established immune system-related diseases. The advancements in molecular biology and genomic/post-genomic sciences point to a comprehensive synthesis of information on the physiology and the pharmacological interventions of “inflammation-related” conditions. Without excluding the decisive character of inflammatory mediators, such as histamine and cytokines, and the latest significant developments in atopy/allergy, autoimmunity and infections, recent evidence provides insights into the participation of related mechanisms in a variety of other common human conditions, including cardiovascular and endocrine diseases, neurological disorders, and cancer; thus expanding the endeavours of immunopharmacological investigation. Interestingly, inflammation and the implicated cells and mediators, nowadays are regarded as “double-edged swords”; a characterization derived from their remarkable duality in favoring immune system function as well as in eliciting inflammatory and pro-inflammatory responses [1-4]. The multi-system modulatory pathways implicated in the polarization of T helper (TH) lymphocytes of the TH1 and TH2 type [5], which are basically considered as regulators of immunostasis in health and disease [6]; and the organ and tissue specific, sometimes unexplained and paradoxical responses of prostaglandins [2] may serve as mere paradigms of the dual character of related endogenous circuits. The basis for these phenomena is not understood adequately, thereby urging the need to identify the homeostatic and self-regulating feedback mechanisms. In this concept, the efficacy, toxicity and drug interactions in therapeutic regiments, involving old and new agents [2, 5], need thorough evaluation, aiming at optimally exploiting the latest data for the development of beneficial end-points. Regarding pharmacological intervention in the endogenous cross-talk, prototype drugs, already under phase II clinical trials, have been directed towards a specific molecular target; yet simultaneously modulating multiple signaling cascades in highly conserved homeostatic pathways, like the cellular stress response [7-10] The articles in this special issue seek (i) to summarize the state-of-the-art in newly recognized mediators of homeostatic mechanisms of the organism; (ii) to explore novel aspects of well established inflammatory cells and mediators; and (iii) by classical and genomic pharmacological studies, to evaluate some current and anticipated anti-inflammatory strategies. These fundamental approaches integrate immunopharmacological data, challenging efficient therapeutic intervention. Commencing with glucocorticoids, the prominent example of drugs developed on an endogenous anti-inflammatory pathway, the article by Prof. Perretti's group [11] elaborates on the most recent research on specific effectors of antiinflammation, like peptides, polyunsaturated fatty acid derivatives and the anti-inflammatory short-lived gases nitric oxide (NO) and carbon monoxide (CO). In order to control inflammatory pathologies, the authors propose that understanding of a given anti-inflammatory circuit would be of great help in developing more efficient drugs that mimic the way our own body assures the inflammatory response. However, long established inflammatory mediators, like histamine, have not been ignored by immunopharmacologists. The discovery of the novel histamine H4 receptor has lead to a reassessment of the role of histamine in several pathophysiological conditions and offered to the amine a new perspective beyond its traditional H1- mediated immunopharmacological properties [12]. Thus, as described by Dr Venable and Dr Thurmond in this issue [12], the H4 receptor could be a good medicinal chemistry target for the rational development of compounds to treat a variety of allergic and inflammatory conditions. Likewise, our group presents recent data on the differentially released pro-inflammatory and antiinflammatory mediators from the somewhat neglected mast cell, that support additional versatile effector roles for these phenotypically diverse components of the immune system, beyond their historical involvement in type I hypersensitivity reactions [13]. Consequently, Prof. Mannaioni's group provides a comprehensive risk-benefit insight not only into the widely prescribed non-steroidal anti-inflammatory drugs (NSAIDs, aspirin; Coxibs like celecoxib, rofecoxib) and acetaminophen, but also into the newly developed NO-NSAIDs or COX-inhibiting NO donors (CINODs) and CO-releasing molecules (CO-RMs) [14].....