Inflammation & Allergy-Drug Targets (Discontinued) - Volume 10, Issue 3, 2011

Nasal polyps (NP) are common benign degeneration of nasal sinus mucosa with a prevalence around 4% in the adult population. The causes are still uncertain but there is a strong association with allergy, infection, asthma and aspirin sensitivity. Histologically, the presence of a large quantity of extracellular fluid, mast cell degranulation and eosinophilia has been demonstrated. Typically the patients show nasal obstruction, anosmia and rhinorrhoea. Nasal endoscopic examination and CT imaging allow evaluation of the disease extention. A combined medical and surgical treatment is recommended for symptoms control in preventing symptomatic NP recurrence. We will review the current knowledge in the pathogenesis and treatment of this complex disease entity.

There may be some difficulties to differentiate Behcet's disease (BD), recurrent aphthosis (RA), and herpetic aphthous ulceration, from other mimicking oral disorders. Despite of unexpected sensitivity and responsiveness, the skin pathergy test regarding a non-specific hypersensitivity has long been thought as one of auxiliary diagnostic benefits for BD. To determine the potential usefulness and disease specificity of the prick reaction with saliva, a skin prick test with neat and filter-sterilized saliva was performed on the forearm skin of 26 individuals; 10 patients with BD (8 incomplete type without uveitis, 1 complete type, and 1 neurological type), 5 with RA, 3 with herpetic oral aphthosis, 2 with erythema nodosum alone, and 6 healthy controls. We assessed the skin reaction at 48 hours after pricking, and the pricked skin lesions were biopsied and analyzed immunohistologically. Nine of 10 BD patients (90 %) exhibited an indurative erythema at the skin site pricked with self-saliva, whereas 3 of 5 RA patients (60%) were relatively weak reaction. Pricking with filter-sterilized saliva failed to recapitulate any of positive skin reactions, albeit a faint erythematous dot appeared in a few BD patients, implicating the involvement of causative microorganism(s) in oral bacterial flora. Culture of saliva from 3 randomly chosen BD patients revealed numerous streptococcal colonies on Mitis-Salivarius agar. Histology of the pricked skin sites showed perivasucular inflammatory infiltrates, composed of CD4+ T cells and CD68+ monocyte/macrophage lineage, a feature consistent with a delayed type hypersensitive reaction. Our results suggested that skin prick test using self-saliva (a new diagnostic pathergy) can be a simple and valuable in vivo diagnostic approach for differentiating BD and RA from other mimicking mucocutaneous diseases. The positive skin prick may be triggered by resident intra-oral microflora, particularly streptococci, and may in part address the underlying immunopathology in BD.

Viral double-stranded RNA (dsRNA) and its synthetic analog poly(I:C) are recognized via multiple pathways and induce the expression of genes related to inflammation. In the present study, we demonstrate that poly(I:C) specifically induced the expression of matrix metalloproteinase-9 (MMP-9) in HaCaT keratinocytes. Studies using specific pharmacological inhibitors revealed the involvement of NF-κB, p38 MAPK, and PI-3K signal transduction pathways in poly(I:C)-induced MMP-9 gene expression. MMP-9 gene induction was sensitive toward treatment with the macrolide antibiotic bafilomycin A1, a vacuolar H+-ATPase inhibitor, and with the lysosomotropic agent chloroquine. However, cycloheximide treatment only partially blocked poly(I:C)-induced MMP-9 gene expression. Although HaCaT keratinocytes produce a number of cytokines and chemokines in response to poly(I:C), stimulation experiments revealed that exclusively TNF-α strongly promoted MMP-9 gene expression. During the antiviral response MMP-9 expression may be of importance for the tissue injury phase.

Asthma is a complex disease characterized by variable airflow limitation, hyperresponsiveness, and airways inflammation. Despite valuable therapeutic advances to control asthma symptoms in the last decade, a quantifiable proportion of patients with moderate to severe asthma continue to experience inadequate disease control, highlighting an important unmet need. In animal models of asthma, interleukin (IL)-9 regulates the development of airway inflammation, mucus production, airway hyperresponsiveness, and airway fibrosis largely by increasing mast cell numbers and activity in the airways. Mast cells are involved in the pathogenesis of eosinophilic and noneosinophilic asthma. Thus, targeting the IL-9 pathway may provide a new therapeutic modality for asthma. The purpose of this review is to summarize the IL-9-mast cell axis in the pathogenesis of asthma and discuss clinical studies with a humanized anti-IL-9 monoclonal antibody, MEDI-528, in subjects with asthma.

Although interleukin-25 (IL-25) has been traditionally considered as a cytokine involved in T helper (Th) 2 cell-associated allergic diseases and host defence against helminthic parasites, recent studies have shown that IL-25 exerts negative effects on the initiation and progression of Th1/Th17-mediated pathologies. This later function of IL-25 is particularly evident at the gut level, where IL-25 could contribute to attenuate tissue-damaging immune responses. These new and exciting pre-clinical observations suggest that therapeutic interventions aimed at enhancing IL-25 activity could be useful in the management of patients with chronic gut inflammation.

To do a bibliographic review of the given association of atopic [AD] and immunological diseases with central nerve system tumors [CNST] described a few years ago and to know the knowledge available. It gives an overview of the studies describing this association, and those explaining its mechanism. A negative association of AD with CNST stands out in case-control studies, which is not observed in cohort studies. The greatest association is seen for gliomas and is less significant for meningiomas. A clearer definition for the AD under study, tumour types, and the exact biochemical and clinical parameters to help diagnoses are the recommended as well as to establish an aetiologic and temporal relationship between AD and CNST.

TLR ligands are present on both commensal and pathogenic microbes. Intestinal epithelial cells (IECs) have been observed to be largely unresponsive to TLR ligands. This observation has partly been explained by the fact that TLR expression on IECs is sparse. The discovery of the Toll-like receptors finally identified the innate immune receptors that were responsible for many of the innate immune functions that had been studied for many years. Interestingly, TLRs seem only to be involved in the cytokine production and cellular activation in response to microbes, and do not play a significant role in the adhesion and phagocytosis of microorganisms. One member of this group, interleukin-1β (IL-1β), together with tumour-necrosis factor (TNF), is defined as an ‘alarm cytokine’. It is secreted by macrophages and initiates inflammation on activation of TLRs.

Type 1 diabetes is an autoimmune disease in which pancreatic beta cells are destroyed by autoreactive T cells. It is a common pediatric disease with increasing incidence. Islet transplantation may be a therapeutic option, however, the current limitations of this procedure mean that for most sufferers of type 1 diabetes there is no cure. The transcription factor NF-κB has been widely studied for its role in development of type 1 diabetes. Recent data have shown that NF-κB is required for activation of autoreactive T cells, and its hyperactivity in monocytes and dendritic cells results in altered cytokine secretion and antigen presentation, which ultimately contributes to the initiation of type 1 diabetes. NF-κB is also activated by a number of proinflammatory cytokines to regulate both the survival and death of beta cells. The critical role of NF-κB in type 1 diabetes renders it a promising pharmaceutical target in the intervention of this disease and further understanding of the NF- κB pathway will have an important implication on the development of novel and safe therapeutic strategies.

Autoimmune responses and inflammation are involved in the pathogenesis of many cardiovascular diseases. There is compelling evidence that inflammatory mechanisms may contribute to progressive heart failure. Thus, myocardial infiltration of lymphocytes and mononuclear cells, increased expression of pro-inflammatory chemokines and cytokines and circulating autoantibodies are frequently observed in myocarditis and dilated cardiomyopathy (DCM). Experimental autoimmune myocarditis (EAM) in rodents may be elicited by immunization of cardiac myosin and EAM in rats mimics human fulminant myocarditis in the acute phase and human DCM in the chronic phase. Our animal model, EAM was demonstrated to progress into the clinicopathological state similar to DCM in the chronic phase, and was found to be characterized by the enlargement of the heart, dilatation of ventricles, diffuse and extensive myocardial fibrosis, besides being a cellular immunity and inflammation mediated disease. Severity of myocarditis was characterized by increased inflammation, cardiac fibrosis and decreased myocardial performance in rats with DCM. Pharmacological interventions such as angiotensin converting enzyme inhibitors (ACEI) and angiotensin receptor blockers (ARBs) significantly attenuated the myosin-induced inflammation and cardiac fibrosis and thereby improving myocardial function in rats with DCM. A growing body of evidence shows that ACEI and ARBs contribute to the pharmaceutical management of patients with heart failure mediated by immune and inflammatory response. The purpose of this review is to emphasize the role of inflammation and myocardial fibrosis in rats with DCM after EAM and study the effects of pharmacological interventions such as ACEI, ARBs in the treatment of heart failure through the suppression of inflammatory cytokines and fibrosis.