Inflammation & Allergy-Drug Targets (v.8, #1)

Editorial by Kurt Zaenker (1-1).
In 2009, the journal and#x201C;Inflammation and Allergy - Drug Targetsand#x201D; starts to publish the 8th volume. Reading the names of excellent and well-recognized scientists - either serving as Regional Editors or being placed as members of the Editorial Advisory Board - it was a pleasure to accept the offer by Bentham Science Publishers Ltd., to overtake for a limited period the position of an Editor-in-Chief. The rapid and continuous upsurge of interesting data from basic, translational and clinical research in the subject of inflammation and allergy, together with visions for novel therapeutic strategies necessitates the publication of this journal. The worldwide contributions at the state-of-the-art science to this journal should furnish the updated and latest news to the researchers, the clinicians and, also to the students, because they have once to succeed into the footstep of all of us. We should ignite a fire of continued interest in all of them by offering a highly ranked platform of rapid communication and nondogmatic discussion. Concepts, methodologies and therapies are ever changing and progress in the areas of inflammation and allergy promises to offer breakthrough in the future in cancer, diabetes, neurological disorders, heart and vascular disease and many other diseases, still in an orphan status in respect to be understood at a molecular level or lacking therapeutic options. Of course, everybody of us experiences during the daily work that publications in science arise tsunami-like, and many of them are disappearing soon after the release of a first couple of volumes. This must not be the case with and#x201C;Inflammation and Allergy - Drug Targetsand#x201D;. All of us, the members of the Editorial Advisory Board, the Regional Editors and the EiC can help with their networks that this journal growths academically, stays open-minded and is totally devoted to search for non-dogmatic truth in medical science - for the sake of patients; everybody of us can be and will be tomorrow a patient.

A Systematic Review of the Potential Herbal Sources of Future Drugs Effective in Oxidant-Related Diseases by Shirin Hasani-Ranjbar, Bagher Larijani, Mohammad Abdollahi (2-10).
Objective: This review focuses on the medicinal plants growing and having history of folk medicine in Iran and found effective as anti free radical damage in animal or human. Design: Embase, Scopus, Pubmed, Web of Science, Google Scholar, IranMedex, and SID databases were searched up to 2 February 2008. The search terms were antioxidant or and#x201C;lipid peroxidationand#x201D; and and#x201C;plant, medicinal plant, herb, traditional, natural or herbal medicineand#x201D; limited to Iran. Studies that assessed effects on cell lines or isolated organs, fetal toxicity, and reviews or letters were excluded. Antioxidative effect and lipid peroxidation inhibition were the key outcomes. Results: Forty-six animal studies on the efficacy of medicinal plants were reviewed. Lipid peroxidation was reduced in different clinical circumstances by Ferula szovitsiana, Nigella sativa, Rosa damascene petal, Phlomis anisodonta, Rosemary, Zataria multiflora Boiss, Saffron, Amirkabiria odorastissima mozaffarian, Ficus carica Linn., Ziziphora clinopoides, Carica papaya, Chichorium intybus, Turmer, Eugenol, Curcumin, and Pistacia vera L. Human studies showed that Cinnamomum zeylanicum and Echium amoenum Fisch and C.A. Mey reduce lipid peroxidation and improve total antioxidant power in healthy subjects. Improvement of blood lipid profile was shown by Silybum marianum, garlic, and wheat germ. Conclusion: Amongst these useful herbs, some like Cinnamon, Silybum marianum, Garlic, Nigella, and Echium seem potential targets of future effective drugs for diseases in which free radical damage play a pathogenical role.

Kounis Syndrome Following Beta-Lactam Antibiotic Use: Review of Literature by Maricel Ridella, Satish Bagdure, Kenneth Nugent, Cihan Cevik (11-16).
Background: Patients with anaphylaxis can have acute coronary syndromes secondary to allergic mediator effects on coronary vessels. Information about these cases is restricted to isolated case reports. Methods: To review this topic we identified all cases in the PubMed database in English with searches using betalactams adverse effects and several coronary disease MeSH terms. Results: We analyzed 17 cases with a median age of 60 (range 13 to 72). Seventy-six percent of the patients were men. The beta-lactam antibiotic was administered by oral, IV, and intramuscular routes. Thirteen patients had cutaneous reactions, seven had respiratory symptoms, two had GI symptoms, 11 had chest pain, and 12 had hypotension. All reactions except one developed within 30 minutes. Ten patients had an elevated troponin levels. ECG revealed ST segment elevation in all patients except one. Cardiac catheterization was normal in 10 patients and abnormal in five patients. Allergy testing identified four patients with positive skin tests to antibiotics, four with increased IgE levels, three with increased histamine and tryptase levels, and one with a positive leukocyte transformation test. Treatment included drugs for anaphylaxis and acute coronary syndrome. All patients survived. Conclusions: Patients with anaphylaxis can present with acute coronary syndrome secondary to either vasospasm or acute plaque rupture and thrombus formation. The typical patient is a man with cutaneous, respiratory and cardiac symptoms and with ST segment elevation in inferior leads. The pathogenesis involves histamine and other mast cell mediators. Management should include therapy for anaphylaxis and vasospasmolytics. The use of epinephrine requires caution.

Adverse reactions after intravascular administration of iodine contrast media are common and prophylactic regiments consisting of the use of steroids and low osmolality contrast media are highly effective in significantly decreasing the adverse reactions rate. The same type of contrast media are also used for opacification of the biliary tree and the pancreatic duct at the time of endoscopic retrograde cholangiopancreatography (ERCP). Systemic absorption of contrast media after ERCP routinely occurs. Although the adverse reaction rate appears to be very low the exact incidence remains unknown due to the retrospective nature of all reports. Despite the lack of formal recommendations, numerous prophylactic regiments are routinely used prior to ERCP in patients with history of prior reaction to intravascular contrast media. Moreover, the use of prophylaxis has even expanded to patients with no prior reaction to intravascular contrast media who are somehow perceived to be at increase risk (e.g. shellfish allergy). Recently, the first large scale prospective study reported exceedingly low incidence of adverse reaction to high oslmolality iodine-containing contrast media administered at the time of ERCP done without prophylactic premedication even in patients considered to be at the highest risk (prior severe reaction to intravascular contrast media administration). These data suggest that the use of prophylactic regiments prior to ERCP appears to be unnecessary.

Arsenic trioxide (As2O3; ATO) is considered to be one of the most potent drugs in cancer chemotherapy and is highly effective in the treatment of acute promyelocytic leukemia (APL). It is well established that treatment of APL patients with ATO is associated with the disappearance of the PML-RARand#945; fusion transcript, the characteristic APL gene product of the chromosomal translocation t(15;17). Although its mode of action is still not fully understood, ATO is known to induce cell apoptosis via generation of reactive oxygen species and activation of caspases. Several reports have indicated that ATO acts principally by inducing cell apoptosis not only in APL, but in a variety of non-APL cells including myeloma cells, chronic myeloid leukemia cells and cells of immune origin, including B or T lymphocytes, macrophages and, more recently, neutrophils. There is an increasing amount of data, including some from our laboratory, concerning the interaction between ATO and human primary cells. The focus of this review will be to cover the role of ATO in human immune primary cells with special emphasis on cells of myeloid origin.

Molecular Basis of the Anti-Inflammatory Effects of Terpenoids by B. Heras, Sonsoles Hortelano (28-39).
Natural products play a significant role in human health in relation to the prevention and treatment of inflammatory conditions. Among them, terpenoids (also referred to as terpenes), are the largest and most widespread class of secondary metabolites. They are found in higher plants, mosses, liverworts, algae and lichens, and also in insects, microbes or marine organisms. Some terpenoids have been used for therapeutic purposes for centuries as antibacterial, antiinflammatory, antitumoral agents, and in recent decades research activity into the clinical potential of this class of compounds has increased continuously as a source of pharmacologically interesting agents. In the present review, molecular basis of the anti-inflammatory action of diterpenoids is presented with special emphasis on their ability to modulate critical cell signaling pathways involved in the inflammatory response of the body such as nuclear transcription factor-kappaB (NF-and#954;B) activation. NF-and#954;B plays an important role in the regulation of immune and inflammatory responses. Indeed, deregulated NF-and#954;B expression is a characteristic phenomenon in several inflammatory diseases and NF-and#954;B has become a major target in drug discovery. Hence, this article also introduces our recently elucidated findings about the potential of labdane diterpenoids as anti-inflammatory agents due to their ability to inhibit NF-and#954;B. The future development of this class of compounds as anti-inflammatory drugs requires the introduction of novel molecular targets of therapeutic relevance in addition to biotechnological approaches for the production of these molecules.

The IL-12 Family of Cytokines in Infection, Inflammation and Autoimmune Disorders by Katrina Gee, Christina Guzzo, Nor Che Mat, Wei Ma, Ashok Kumar (40-52).
Cytokines are critical coordinators of the immune response necessary for resolving bacterial and viral assaults on the immune system. In particular, the IL-12 family of cytokines are key players in the regulation of T cell responses. These responses are orchestrated by monocytes, macrophages, and dendritic cells which produce the members of the IL- 12 family of cytokines in response to infection. IL-27 and IL-23 are two cytokines that are related to IL-12; these cytokines share homology at the subunit, receptor, and signalling levels. IL-12 is composed of p35 and p40 subunits, which, when combined together form the bioactive IL-12p70. IL-23 is composed of the IL-12p40 subunit as well as the IL-23p19 subunit, which shares homology with IL-12p35. IL-27 is composed of EBI3 and p28. These three cytokines activate similar members of the JAK/STAT signalling pathways as a result of homology in their receptor components. Production of these cytokines by activated monocytes, macrophages, and dendritic cells results in the activation and differentiation of T cells. In spite of their similarity, each of these cytokines has specific roles in the regulation of immune responses. IL-12 is required for the induction of IFN-and#947; production, critical for the induction of Th1 cells. IL-27 has been shown to play a role in the induction of Th1 cells from naive T cells, whereas IL-23 has been demonstrated to play a key role in the induction of the newly described Th17 cells. Recently, a novel heterodimeric and anti-inflammatory cytokine composed of the IL- 12p35 and EBI3 subunits has been identified as IL-35. The biological properties of the IL-12 family of cytokines, the signalling pathways mediated by these cytokines and their role in infection, inflammation, and autoimmune diseases will be the focus of this review.

TNF-α in Tuberculosis: A Cytokine with a Split Personality by Amanda Mootoo, Elena Stylianou, Mauricio Arias, Rajko Reljic (53-62).
TNF-and#945; is an essential component of the innate defence mechanism of the host against pathogenic challenge. Unfortunately, it can also play a major role in the pathology of certain diseases, such as tuberculosis. This disease is a striking example of the role of TNF-and#945; as a and#x2018;double-edged swordand#x2019;, because apart from its role in controlling the Mycobacterium tuberculosis infection, it can also cause severe tissue damage. TNF-and#945; exhibits a very complex network of interactions and many of its activities are still not fully understood. This report aims to review the pivotal role of TNF-and#945; in controlling the mycobacterial infection, with a particular emphasis on its influence on chemokine expression and cell movement during granuloma formation, and the issues surrounding the use of TNF-and#945; inhibitors for therapeutic use in inflammatory diseases.

Inflammatory Mediators in Smoke Inhalation Injury by James Sterner, Thomas Zanders, Michael Morris, Leopoldo Cancio (63-69).
Smoke inhalation occurs in 10and#x25; to 30and#x25; of patients admitted to burn centers, and increases mortality by a maximum of 20and#x25; over that predicted by age and extent of cutaneous burn alone. Pneumonia in these patients then further increases mortality by a maximum of 40and#x25;. While one estimate suggested that 75and#x25; of deaths following burn injury may be accounted for by inhalation injury, more recent cohort studies have suggested there is a decreasing mortality attributable to inhalation injury. As part of understanding and improving outcomes from burn injuries, the pathophysiology and inflammatory processes involved in smoke inhalation injury has been extensively investigated in animal models. This review will emphasize the inflammatory pathways involved in inhalation injury, and targeted methods used to treat this injury in both experimental and human models.

Renal & Ocular Targets for Therapy in Wegener's Granulomatosis by Lavnish Joshi, Sally Hamour, Alan Salama, Charles Pusey, Sue Lightman, Simon Taylor (70-79).
Wegener's granulomatosis (WG) is a multisystem small-vessel vasculitis which is characterised by granulomatous inflammation. Respiratory tract involvement is most commonly seen, affecting up to 85and#x25; of patients, closely followed by the renal system in up to 75and#x25; of patients; ocular involvement in WG is estimated to occur in 50-60and#x25; of patients. The purpose of this review is to provide an overview of the renal and ocular manifestations of WG and discuss the rationale behind the therapeutic approach. In particular, we will focus on how understanding the disease processes in both of these organs has led to more targeted therapy. The mechanism of action of the various immunosuppressive medications in both systemic and ocular inflammation and the evidence available for their use will also be discussed.

Role of Fc Receptors as a Therapeutic Target by Atsuhiro Masuda, Masaru Yoshida, Hideyuki Shiomi, Yoshinori Morita, Hiromu Kutsumi, Hideto Inokuchi, Shigeto Mizuno, Akira Nakamura, Toshiyuki Takai, Richard Blumberg, Takeshi Azuma (80-86).
It has been forty years since the discovery of Fc Receptors and their function. Fc Receptors include the IgG receptors (Fcand#947;R), high-affinity IgE receptor (Fcand#951;RI), IgA and IgA/IgM receptors, and neonatal Fc receptor for IgG (FcRn). In particular, the Fcand#947;Rs have been well known to play an important role in many biologic processes including those associated with the response to infection and cancer as well as in the pathogenesis of immune-mediated diseases. Both positive and negative regulatory function has ascribed to Fc receptors and Fcand#947;Rs in particular which serve to establish a threshold for immune cell activation. In other cases, Fc receptors such as FcRn possess a novel structure and function by playing a major role in the transport of IgG across polarized epithelial barriers at mucosal surfaces and in the regulation of IgG halflife. These diverse functions highlight the potential effectiveness of targeting Fc receptors for therapeutic purposes. This review summarizes new information available in the therapeutic applications of this biology.