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Immunosuppressive Molecules (immunosuppressive + molecule)
Selected AbstractsLocalized erosive pustular dermatosis of the scalp at the site of a cochlear implant: successful treatment with topical tacrolimusCLINICAL & EXPERIMENTAL DERMATOLOGY, Issue 5 2009A. V. Marzano Summary Erosive pustular dermatosis of the scalp (EPDS) is a rare form of nonmicrobial pustulosis mainly occurring in elderly patients with long-term sun damage to the skin. Clinically, it is characterized by pustular lesions that progressively merge into erosive and crusted areas over the scalp. The histology of EPDS is nonspecific, and its pathophysiology remains undetermined, with various types of local trauma possibly acting as the triggering factor. We describe a 24-year-old woman who developed EPDS after cochlear implant surgery for profound sensorineural hearing loss. We speculate that either the cutaneous surgery during cochlear implantation or the skin inflammation that commonly occurs near the magnet might have triggered the disorder. It is of note that the patient's skin lesions healed completely after treatment with topical tacrolimus, a relatively novel immunosuppressive molecule. Thus, topical tacrolimus may be indicated as a therapeutic alternative to the widely used steroids for this disease, mainly to avoid steroid-related cutaneous atrophy. [source] Frequent overexpression of multiple ErbB receptors by head and neck squamous cell carcinoma contrasts with rare antibody immunity in patientsTHE JOURNAL OF PATHOLOGY, Issue 3 2004Roberto Bei Abstract In an effort to elucidate the role of ErbB receptors in human head and neck squamous cell carcinoma (HNSCC), expression abnormalities and subcellular localization of epidermal growth factor receptor (EGFR), ErbB2, ErbB3, and ErbB4 were investigated along with EGF and tenascin by immunohistochemistry in 38 carcinomas as compared to adjacent normal mucosa of 24 cases. Although tumour-specific overexpression affected each ErbB receptor (EGFR 47%, ErbB2 29%, ErbB3 21%, ErbB4 26%), EGFR abnormalities were most prevalent. The latter, and overexpression of more than two ErbB receptors in the same tumour, which always included EGFR, correlated with metastatic disease. ErbB products were specifically detected on the cell membrane and in the cytoplasm. In contrast, ErbB4 was uniquely localized to the nucleus in 7 carcinomas and a tumour-derived cell line, indicating a role for regulated intramembrane proteolysis resulting in nuclear ErbB4 translocation in HNSCC. Expression of prototype ligand EGF or low-affinity stromal activator tenascin correlated significantly with EGFR overexpression, implying chronic EGFR activation. Simultaneous overexpression of additional ErbB receptors in most of these cases suggested recurrent involvement of receptor heterodimers. In spite of frequent ErbB receptor alterations, autologous ErbB serum antibodies were rare, with only 1 of 38 tumour patients exhibiting an ErbB2-specific immune response. Based on upregulation of several known immunosuppressive molecules, scarcity of ErbB-specific antibodies is consistent with attenuation of natural tumour-specific immune responses in HNSCC. Copyright © 2004 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. [source] Cannabinoid control of neuroinflammation related to multiple sclerosisBRITISH JOURNAL OF PHARMACOLOGY, Issue 5 2007D Baker The cannabis plant (Cannabis sativa) has been known by many names but the question remains ,Can we call it medicine?' There has been renewed interest in the value of cannabis for the control of neuroinflammatory conditions such as multiple sclerosis, where it has been shown to have some effect on spasticity and pain both experimentally and in clinical trials in humans. However, in addition to symptom control potential, the question remains whether cannabinoids can modify the neuroinflammatory element which drives relapsing neurological attacks and the accumulation of progressive disability. In experimental studies it has been recently shown that synthetic cannabinoids can affect the immune response both indirectly via CB1 receptor-mediated signalling nerve centres controlling the systemic release of immunosuppressive molecules and directly by CB2 receptor-mediated inhibition of lymphocyte and macrophage/microglial cell function. However, these immunosuppressive possibilities that would limit the frequency of relapsing attacks will probably not be realized clinically, following use of medical cannabis, due to dose constraints. However, cannabinoids may still affect the glial response within the damaged central nervous system, which facilitate the slow, neurodegenerative processes that account for progressive neurodegeneration, and therefore may have utility in addition to value of cannabis-related drugs for symptom control. British Journal of Pharmacology (2007) 152, 649,654; doi:10.1038/sj.bjp.0707458; published online 24 September 2007 [source] Principles of immunosuppression in uveitisACTA OPHTHALMOLOGICA, Issue 2009F WILLERMAIN Non infectious uveitis is a heterogeneous group of diseases mediated through autoimmune and autoinflammatory mechanisms. It is thus crucial to perform a complete work-up to characterise the disease and eventually find a precise aetiology or a systemic associated condition. When the inflammation is bilateral and the vision threatened, systemic drugs are usually proposed. Despite tremendous progress in the understanding of the disease, treatments are generally based on the administration of non specific immunosuppressive molecules. Currently, high doses oral corticosteroids are first given, followed by a slow tapering of the dosage. If this strategy does not lead to disease control, a steroid-sparing agent should be considered. Antimetabolites, T-cell inhibitor and alkylating agents will be chosen (alone or in combination), depending on the severity of the disease and patients general status. Recently the development of biologic agents offers the possibility to target various specific molecules important in non infectious uveitis development. Nowadays, anti-TNF, have been mostly tested with encouraging results. However, it is likely that different uveitis subtypes would require different biologic agents. In the future, the growing production of specific inhibitors might lead to a more tailored approach of uveitis treatment. [source] Immune regulatory effects of simvastatin on regulatory T cell-mediated tumour immune toleranceCLINICAL & EXPERIMENTAL IMMUNOLOGY, Issue 2 2010K. J. Lee Summary Statins are potent inhibitors of hydroxyl-3-methylglutaryl co-enzyme A (HMG-CoA) reductase, and have emerged as potential anti-cancer agents based on preclinical evidence. In particular, compelling evidence suggests that statins have a wide range of immunomodulatory properties. However, little is known about the role of statins in tumour immune tolerance. Tumour immune tolerance involves the production of immunosuppressive molecules, such as interleukin (IL)-10, transforming growth factor (TGF)-, and indoleamine-2,3-dioxygenase (IDO) by tumours, which induce a regulatory T cell (Treg) response. In this study, we investigated the effect of simvastatin on the production of IL-10, TGF-, and IDO production and the proliferation of Tregs using several cancer cell lines, and Lewis lung cancer (3LL) cells-inoculated mouse tumour model. Simvastatin treatment resulted in a decrease in the number of cancer cells (3LL, A549 and NCI-H292). The production of the immune regulatory markers IL-10, TGF-, in 3LL and NCI-H292 cells increased after treatment with simvastatin. The expression of IDO and forkhead box P3 (FoxP3) transcription factor was also increased in the presence of simvastatin. In a murine 3LL model, there were no significant differences in tumour growth rate between untreated and simvastatin-treated mice groups. Therefore, while simvastatin had an anti-proliferative effect, it also exhibited immune tolerance-promoting properties during tumour development. Thus, due to these opposing actions, simvastatin had no net effect on tumour growth. [source] | ||||||||||