Inflammation & allergy drug targets最新文献

Acne is a chronic self-limited disease, which affects mostly teenagers, without gender difference. In recent years, the incidence has increased in female adults. The factors involved in this epidemiological observation are still under discussion in the literature. Clinically, acne is characterized by different types of lesions. The disease affects the regions rich in sebaceous glands (face, chest and upper back). The clinical lesions are: open and closed comedones, erythematous papules, pustules, nodules and different types of scars. Taking into consideration the general concept of inflammation (redness, pain, heat and loss of function), acne is traditionally classified as non-inflammatory (open and closed comedones) and inflammatory (other primary lesions). With the knowledge advancement this concept seems to be wrong and therefore acne would be an inflammatory disease even before the onset of their clinical lesions.

Dengue fever is a mosquito-borne viral disease infecting several hundred million people in tropical and subtropical areas every year. Its clinical manifestations range from mild fever to severe life-threatening shock syndrom. No therapeutics or licensed vaccines are available yet and with half of the world's population already at risk, it represents a major public health concern. The co-existence of four different Dengue virus serotypes renders difficult the obtaining of full protective immunity against each one of them. On the contrary, these serotypes trigger significant cross-reactivities of antibodies and T cells, both of which may lead to disease enhancement when reactivated in the context of reinfection with a heterologous serotype. Several immunological concepts have been developed to explain disease enhancement, and the uncertainty around the topic has consequently slowed down the development of Dengue vaccines. Recent advances however have shed light on key aspects of both the immunoprotective and immunopathological mechanisms. In particular the responses of specific antibodies and T cells have been a focus of many studies. These immunological players are thought to directly influence a cytokine dysbalance that eventually leads to severe disease and vascular leakage. In this review I outline current concepts and ongoing debates on the above topics. A better understanding of Dengue virus immunopathogenesis is critically needed to optimize candidate vaccines including those currently under development. In particular, the results from large-scale human efficacy trials will offer outstanding opportunities to refine correlates of protection and design even more effective vaccines.

Background/purpose(s): There is a growing interest in the targeting of Toll-like receptors (TLRs) for the treatment of allergic diseases. TLRs7/8 ligands are future candidates of therapeutic value in allergic rhinitis (AR). This study focus on TLRs7/8 ligand; resiquimod (R848) as an adjuvant to immunotherapy (IT) in AR patient.

Methods: Peripheral blood mononuclear cells (PBMCs) were obtained from atopic donors and non atopic donors. PBMCs were cultured in the absence and presence of date palm pollen allergen (Phoenix dactylifera; Pho d) and/or R848. Interleukin-4 (IL-4), IL-10, IL-13 and interferon gamma (IFN-γ) were measured in the culture supernatants.

Results: R848 was able to significantly increase the anti-inflammatory response in atopic donors more than non atopic donors. Nevertheless, the combination of both; R848 and Pho d provides inferior stimulus as compared to R848 alone in both atopic and non atopic donors.

Conclusion: Invitro treatment of PBMCs with R484 hijacks the pro inflammatory immune process triggered by TLRs7/8 to mediate anti-inflammatory response. This may provide a conception about the activity and efficacy of TLRs7/8 ligands in AR and open the gate for them to be applied in clinically in humans.

Chronic pain is a debilitating condition and, in most cases, difficult to treat. A prominent example of this is neuropathic pain. Understanding pathophysiological mechanisms of pain and, therefore, making this knowledge into an effective treatment is still a challenge to experts. Pain can now be considered as a neuro-immune disorder, since recent data indicate critical involvement of innate and adaptive immune responses following injury, and this interaction plays an important role in the onset and perpetuation of chronic pain. The aim of this article is to review the relationship between immune system and chronic pain, especially about neuropathic pain, and focusing on cytokines, chemokines and lymphocytes.

Chronic infection with hepatitis C virus (HCV) is associated with a large spectrum of extrahepatic manifestations (EHMs), mostly immunologic/rheumatologic in nature owing to B-cell proliferation and clonal expansion. Neurological complications are thought to be immune-mediated or secondary to invasion of neural tissues by HCV, as postulated in transverse myelitis and encephalopathic forms. Primarily axonal neuropathies, including sensorimotor polyneuropathy, large or small fiber sensory neuropathy, motor polyneuropathy, mononeuritis, mononeuritis multiplex, or overlapping syndrome, represent the most common neurological complications of chronic HCV infection. In addition, a number of peripheral demyelinating disorders are encountered, such as chronic inflammatory demyelinating polyneuropathy, the Lewis-Sumner syndrome, and cryoglobulin-associated polyneuropathy with demyelinating features. The spectrum of demyelinating forms also includes rare cases of iatrogenic central and peripheral nervous system disorders, occurring during treatment with pegylated interferon. Herein, we review HCV-related demyelinating conditions, and disclose the novel observation on the significantly increased frequency of chronic demyelinating neuropathy with anti-myelin-associated glycoprotein antibodies in a cohort of 59 consecutive patients recruited at our institution. We also report a second case of neuromyelitis optica with serum IgG autoantibody against the water channel aquaporin-4. The prompt recognition of these atypical and underestimated complications of HCV infection is of crucial importance in deciding which treatment option a patient should be offered.

Cell mediated immunity is the most important response against Mycobacterium tuberculosis (MTB). Regulatory T cells (Treg) play a vital role in suppressing the effector T cell response in tuberculosis (TB) patients. Forkhead box protein 3 (Foxp3) is an important regulator of Treg cells development and function. In this study, we showed that the expression of Foxp3 gene in Treg cells is increased in patients with active tuberculosis. In a case-control study, 183 TB patients and 183 controls were recruited according to ethnicity, gender and living area. Then, after isolation of peripheral blood mononuclear cells (PBMCs), FoxP3 gene expression was studied by real-time PCR. The expression of this gene in patients with pulmonary and extra-pulmonary tuberculosis was 2.8 fold higher than normal subjects (CI=1.29±2.37, P≤0.001). Also comparing the patients with pulmonary tuberculosis and the control group, a significant difference was observed (CI=1.81±2.96, P≤0.001). FoxP3 gene expression was 1.5 fold higher in women with pulmonary and extrapulmonary tuberculosis than in men with tuberculosis (CI=0.12±2.01, P=0.02). According to this study, the increased Foxp3 gene expression in patients with TB was observed and this may play as a contributing factor to suppression of Th1-type immune responses.

The renin-angiotensin system (RAS) conceived as a coordinated hormonal cascade plays an important role in controlling multiple functions in many organs and is much more complex than previously thought. The RAS has continued to expand, with the identification of new components, functions and subsystems. Angiotensin-converting enzyme (ACE) and its novel homolog angiotensin converting enzyme 2 (ACE2) are two key enzymes involved in the synthesis of bioactive components of the RAS. The main active peptides of the RAS include angiotensin II (Ang II), Ang III, Ang IV, and angiotensin-(1-7) [Ang-(1-7)] among which Ang II and Ang-(1-7) are much more important in health and disease. The axis formed by ACE2 represents an endogenous counter-regulatory pathway within the RAS, and its actions are opposite to those of the ACE axis. Conventionally the RAS has been considered to be important in the cardiovascular system, metabolism, cell growth and homeostasis. In recent years, a key role of ACE and ACE2 and their peptides has been recognized in the inflammatory process in conditions such as cardiac hypertrophy, pulmonary hypertension, glomerulonephritis, lung injury, sepsis, and acute pancreatitis. Investigations are ongoing to better understand the role of the RAS in inflammation. A comprehensive understanding of the RAS components in inflammation can provide new possibilities for therapeutic approaches against inflammatory diseases. In this review, we discuss our current understanding of the subject, based on recent findings, on the role of ACE and ACE2 in inflammation.

Adaptation of the whole microbial normal flora residing in a host to its natural habitat over an evolutionary peroid has resulted in peaceful coexistence with mutual benefits for both microbiota and host in steady state. This symbiotic relationship between host and microbiota has a significant impact on shaping the immune response in the host to achieve an immune tolerance to microbiota but retaining the ability to respond to invading pathogens. Perturbation of this balance by manipulation of microbial communities in the host can lead to immune dysregulation and susceptibility to diseases. By studying the host in the absence of microbiota or with alteration of microbiota the complexity of microbial impact on the immune system can be resolved. Conversely, the study of microbiota in the absence of immune system factors can show how the immune system contributes to preservation of the host-microbiota balance. The absence of molecules involved in innate or adaptive immunity in knockout models can perturb the balance between host and microbiota further adding to more immune dysregulation. A better understanding of Microbiome-immune system interaction provides a new opportunity to identify biomarkers and drug targets. This will allow the development of new therapeutic agents for modulating the immune system to improve health with little or no toxicity. The study of interplay between host and microbiota has a promising role in the design of therapeutic interventions for immunopathological diseases arising from imbalanced host and microbiota interactions.

The skin and its immune system manifest a decline in physiologic function as it undergoes aging. External insults such as ultraviolet light exposure cause inflammation, which may enhance skin aging even further leading to cancer and signs of photoaging. There is a potential role for botanicals as an adjunct modality in the prevention of skin aging. Numerous over-the-counter anti-aging products are commercially available, many of which boast unverified claims to reduce stress, inflammation and correct signs of aging. In this article we reviewed the scientific literature for data on frequently published "anti-inflammaging" additives such as vitamins A, C and E and green tea. We also analyzed the evidence available on five promising ingredients commonly found in anti-aging products, namely, argan oil, rosemary, pomegranate, Coenzyme Q10, and Coffeeberry. Though there may be an increasing amount of scientific data on a few of these novel botanicals, in general, there remains a lack of clinical data to support the anti-aging claims made.

Antineutrophil cytoplasmic antibody (ANCA)-related vasculitis is a systemic small-vessel vasculitis, including 3 clinical syndromes: granulomatosis with polyangiitis, known as Wegener's granulomatosis (WG), microscopic polyangiitis (MPA) and the Churg-Strauss syndrome (CSS). ANCA-related vasculitis usually presents with severe kidney or pulmonary disease, has a mortality of 28% at 5 years, and also contributes to increased morbidity in vasculitis patients. Cardiac involvement in this entity may have different forms, including coronary vessels, pericarditis, myocarditis, endocarditis, myocardial infarction and subendocardial vasculitis that can contribute to reduced life expectancy. Cardiovascular magnetic resonance using oedema and fibrosis imaging can early reveal, noninvasively and without radiation, heart involvement during vasculitis, undetected by other imaging techniques and guide further risk stratification and treatment of these patients.