Inflammation & Allergy-Drug Targets (Discontinued) - Volume 9, Issue 3, 2010

Histamine has been demonstrated to be involved in cell proliferation, embryonic development, and tumour growth. These various biological effects are mediated through the activation of specific histamine receptors (H1, H2, H3, and H4) that differ in their tissue expression patterns and functions. Although many in vitro and in vivo studies of the modulatory roles of histamine in tumour development and metastasis have been reported, the effect of histamine in the progression of some types of tumours remains controversial; however, recent findings on the role of histamine in the immune system have shed new light on this question. This review focuses on the recent advances in understanding the roles of histamine and its receptors in tumour biology. We report our recent observations of the anti-tumoural effect of H1 histamine antagonists on experimental and human melanomas. We have found that in spite of exogenous histamine stimulated human melanoma cell proliferation, clonogenic ability and migration activity in a dose-dependent manner, the melanoma tumour growth was not modulated by in vivo histamine treatment. On the contrary, terfenadine-treatment in vitro induced melanoma cell death by apoptosis and in vivo terfenadine treatment significantly inhibited tumour growth in murine models. These observations increase our understanding of cancer biology and may inspire novel anticancer therapeutic strategies.

Idiopathic pulmonary fibrosis (IPF) is a chronic condition of unknown aetiology with deteriorating respiratory function leading to respiratory failure. Sequential acute lung injury leads to progressive fixed tissue fibrosis, architectural distortion and loss of function. An excess of profibrotic cytokines and/or a deficiency in antifibrotic cytokines have been implicated in the pathological process as has excessive oxidation. At present no specific therapy is available. Corticosteroids alone or in combination with immunosuppressive drugs such as azathioprine, colchicine, and cyclophosphamide have been used with limited success. Interferon-gamma-1b showed a significant improvement in pulmonary function only in one study. Pirfenidone, cyclosporine and acetylcysteine may also prove to be of benefit but data from studies are limited. Novel drugs, mainly antifibrotic, anticytokine and immunoregulatory, are currently being investigated in various trial phases. Most recently, endothelin receptor antagonists (e.g., bosentan) have been shown to have possible beneficial effects in early stages of IPF. After a short overview on the current hypothesis on pathophysiology in IPF this review will discuss the present and possible future therapeutic options in IPF.

Allergic inflammation is the result of a specific pattern of cellular and humoral responses leading to the activation of the innate and adaptive immune system which, in turn, results in physiological and structural changes affecting target tissues such as the airways and the skin. Eosinophils activation and production of soluble mediators such as IgE antibodies is a pivotal feature in the pathophysiology of allergic diseases. In the past few years, however, convincing evidence has shown that neurons and other neurosensory structures are not only a target of the inflammatory process but also participate in the regulation of immune responses by actively releasing soluble mediators. The main products of these activated sensory neurons are a family of protein growth factors called neurotrophins. They were first isolated in the central nervous system and identified as important factors for the survival and differentiation of neurons during fetal and post-natal development as well as neuronal maintenance later in life. Four members of this family have been identified and well defined: nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), neurotrophin 3 (NT-3), and neurotrophin 4/5 (NT-4/5). Neurotrophins play a critical role in the bidirectional signaling mechanisms between immune cells and the neurosensory network structures in the airways and the skin. Pruritus and airway hyperresponsiveness (AHR), two major features of atopic dermatitis and asthma, respectively, are associated with the disruption of the neurosensory network activities. In this review we provide a comprehensive description of the neuroimmune interactions underlying the pathophysiological mechanisms of allergic and inflammatory diseases.

Factors related to diet and life style have been identified as primary determinants in about 80% of colorectal cancers. Non-steroidal anti-inflammatory drugs (NSAID) and selective cyclooxygenase-2 (COX-2) inhibitors (COXIB) reduce the relative risk of colon cancer. To overcome systemic COX inhibition associated with NSAID and COXIB, there is a growing interest in developing alternative colon cancer prevention strategies using diet-based approaches that target COX-2. The transition from aberrant crypt foci (ACF) to colon cancer is a multiyear process providing opportunities for nutritional targeting of genes influencing the course of this disease process at early stages of development. The activation of the proinflammatory gene COX-2 and PG production in the colonic mucosa are recognized risk factors in colon cancer. Many natural food components may impact colon cancer risk by interfering with ligand-activated receptors, signal transduction pathways, and transcription factors involved in stimulation of COX-2 expression. In this review, we highlight key upstream features of signaling pathways and transcriptional control of the COX-2 gene and discuss opportunities for dietary modulation of COX-2 expression in gastro-intestinal cancers with special emphasis on prevention of colorectal tumors. Review of the experimental evidence suggests that dietary strategies based on specific or cocktails of bioactive food components as well nutritional-pharmacological combinations targeted to regulation of COX-2 expression and activity may prove useful in the prevention of colon cancer. An integrated approach may offer the advantage of combined higher efficacies. Future studies should investigate the efficacy of combinations of bioactive food compounds on epigenetic regulation of the COX-2 gene and characterize potential synergies and amplification effects resulting from the concomitant use of bioactive food components and COX-2 inhibitors.

The number of children suffering from atopic eczema has increased over the past 30 years especially in children between the ages of 2 and 5 years. There is a significant group of eczematous children that are resistant to standard therapy. Babies and children with eczema suffer pain, irritation and disfigurement from the dermatitis. In this study, we have followed 14 cases of pediatric patients (ages of 8 months to 64 months) with a history of resistant eczema for a period of at least six months. All of these children received 300 mg to 500 mg standardized Lactobacillus rhamnosus cell lysate daily as an immunobiotic supplement. The results of this open label non-randomized clinical observation showed a substantial improvement in quality of life, skin symptoms and day- and nighttime irritation scores in children with the supplementation of Lactobacillus rhamnosus lysate. There were no intolerance or adverse reactions observed in these children. Lactobacillus rhamnosus cell lysate may thus be used as a safe and effective immunobiotic for the treatment and prevention of childhood eczema and possible other types of atopy (allergic diseases).

Nuclear factor-κB (NF-κB) is one of the most important transcription factors; it has a key role in inflammatory and immune responses, cell adhesion, developmental signals, and anti-apoptosis process. Inflammatory lung diseases such as asthma and chronic obstructive pulmonary disease (COPD) are major causes of morbidity and mortality worldwide. In this review, we highlight the role of NF-κB in inflammatory lung disease, the strategies which block the activation of NF- κB, and the therapeutic approaches to treating inflammatory lung disease.

Hypersensitivity reactions to chemotherapy agents are defined as unexpected reactions with signs and symptoms not consistent with known toxicity of these drugs. These reactions range from mild to life-threatening and are difficult to predict. Symptoms include flushing, nausea, difficulty breathing, back pain, hypotension and tachycardia. Hypersensitivity is commonly encountered owing to the increasing use of chemotherapy drugs in clinical practice. The pathogenetic mechanisms are not fully understood but they seem to vary between agents. Reactions to taxanes usually occur during the first few minutes of the first or second infusion, whereas acute reactions to platinum agents usually occur after multiple cycles of therapy. Basic principles that allow management and possible completion of the regimen should be followed. Certain protocols aim to prevent acute reactions by slowing the infusion rate and by administering steroid and histamine receptor antagonists. Skin testing and desensitization protocols have also been successfully used in case of hypersensitivity to various chemotherapy drugs. Knowledge of all available management options assists physicians in making the most appropriate decision regarding further treatment.