Objective. The sympathetic nervous system (SNS) seems to play a proinflammatory role in the early asymptomatic phase of arthritis, but its role in the late stages of chronic arthritis is not well known. The purpose of this study was to examine the effects of the SNS on late-stage chronic arthritis in mice with type II collagen-induced arthritis (CIA).Methods. We tested the effects of the SNS by ablating sympathetic nerves at different time points in mice with CIA. Early sympathectomy was performed 7 days before immunization. Late sympathectomy was performed on day 56. Cytokine stimulation assays were performed on local lymph node cells and spleen cells, and levels of interleukin-10 (IL-10), IL-4, tumor necrosis factor ␣ (TNF␣), and interferon-␥ (IFN␥) were determined.Results. Animals with CIA that underwent early sympathectomy showed significantly lower arthritis scores than the controls. In contrast, animals that underwent late sympathectomy had significantly increased arthritis scores compared with controls. On day 0, lymph node cells from animals subjected to early sympathectomy had increased levels of IL-10 and IL-4 and unchanged levels of TNF␣ and IFN␥ compared with those from untreated animals. This indicates an immune-stimulating property of the SNS in draining lymph nodes. On day 80, lymph node cells and spleen cells from animals subjected to late sympathectomy showed increased levels of TNF␣ and IFN␥ compared with those from nonsympathectomized controls with CIA. This indicates an immune-depressing property of the SNS in draining lymph nodes and spleen. Arthritis per se largely diminished sympathetic nerve fiber density in synovium on day 80 (P < 0.01).Conclusion. The effect of the SNS is bimodal, enhancing or depressing levels of proinflammatory and antiinflammatory cytokines. This feature is dependent on the time point of immune system activation and the respective compartment. The SNS supports inflammation during the asymptomatic phase of CIA, whereas it inhibits inflammation during the chronic symptomatic phase.Since the work of Selye in the 1940s (1), the sympathetic nervous system (SNS) together with the hypothalamic-pituitary-adrenal axis has been thought to play an important supportive role in the fight-or-flight response during stressful events. In linking this important concept to inflammatory diseases, several groups of investigators working from 1960 to the late 1980s delineated a proinflammatory role of the SNS for the early inflammatory response (for review, see ref.2). Indeed, the SNS seems to be a critical proinflammatory component of neurogenic inflammation, which is particularly evident during the first hours after induction of joint inflammation (3), when the SNS mediates an increase in vessel leakage, plasma extravasation, migration of leukocytes to inflamed tissue. This is accompanied by stimulation of sensory nerve fibers (2).At the beginning of the 1980s, with the introduction of in vitro immune cell culture assays that could continue for several days and with the detection of Sup...

The nervous system in the intestine controls motility, secretion, sensory perception, and immune function. Peptidergic neurones with neurotransmitters such as substance P and nerve growth factors have been the main focus of neuroimmunomodulation research in the gut. This review summarises the present knowledge concerning the role of the sympathetic nervous system (SNS) in modulating intestinal inflammation. The role of the SNS for gut inflammation is compared with its role in rheumatoid arthritis which demonstrates notable similarities. Nerve fibres of the SNS not only enter the enteric plexuses but also innervate the mucosa and gut associated lymphoid tissue (GALT). The SNS has pro- and anti-inflammatory functions. Neurotransmitters such as norepinephrine, adenosine, and others can evoke remarkably different opposing effects depending on concentration (presence of sympathetic nerve fibres and extent of neurotransmitter release), receptor affinity at different receptor subtypes, expression of adrenoceptors, availability of cotransmitters, and timing of SNS activity in relation to the inflammatory course. This review attempts to integrate the different perspectives of the pro- and anti-inflammatory effects of the SNS on inflammatory disease of the gut.

The German guideline for the treatment of psoriasis vulgaris was updated using GRADE methodology. The guideline is based on a systematic literature review completed on December 1, 2016, and on a formal consensus and approval process. The first section of this short version of the guideline covers systemic treatment options considered relevant by the expert panel and approved in Germany at the time of the consensus conference (acitretin, adalimumab, apremilast, cyclosporine, etanercept, fumaric acid esters, infliximab, methotrexate, secukinumab and ustekinumab). Detailed information is provided on the management and monitoring of the included treatment options.

Herpes simplex virus type 1 (HSV-1) is resistant to the antiviral effects of interferon (IFN)-alpha, -beta, or -gamma. The fact that ICP0(-) mutants replicate like wild-type virus in IFN-alpha/beta receptor knockout mice (Leib et al., 1999, J. Exp. Med. 189, 663) suggested that ICP0 may serve a direct role in the resistance of HSV-1 to IFN. To test this hypothesis, the effects of IFN-alpha, -beta, and -gamma were compared against wild-type HSV-1 and an ICP0(-) mutant virus, 7134. In Vero cells, 7134 was more sensitive to inhibition by low doses of type I IFN (-alpha/beta) or type II IFN (-gamma) than vesicular stomatitis virus, a well-studied IFN-sensitive virus. At a concentration of 100 U/ml, IFN-alpha, -beta, or -gamma reduced the efficiency of 7134 plaque formation by 120-, 560-, and 45-fold, respectively. In contrast, none of the IFNs reduced wild-type HSV-1 plaque formation by more than 3-fold. Even when Vero cells were infected with 10 pfu per cell, IFN-alpha and -beta inhibited 7134 replication by over 100-fold, but inhibition by IFN-gamma decreased to less than 10-fold. While IFN-beta efficiently inhibited 7134 replication in primary mouse kidney and SK-N-SH cells, IFN-gamma did not inhibit 7134 to a comparable extent in these cells. ICP0 provided in trans from an adenovirus vector allowed 7134 to replicate efficiently in Vero cells in the presence of IFN-alpha, -beta, or -gamma. While IFN-beta or -gamma efficiently repressed the ICP0 promoter-lacZ reporter gene in 7134 (i.e., approximately 60-fold reduction in beta-galactosidase activity), ICP0 provided in trans almost completely reversed IFN-mediated repression of the lacZ gene in 7134. The results suggest that the rate of ICP0 expression in infected cells in vivo may be critical in determining whether host IFNs repress the HSV-1 genome. This concept is discussed in light of its potential relevance to the establishment of latent HSV-1 infections.