The below list represents only planned manuscripts. Some of these
manuscripts have not been received by the Editorial Office yet. Papers
submitted to MDPI journals are subject to peer-review.
Title: Sex-hormone mediation of immune function as a driver of ME/CFS severity
Authors: Jeanna Harvey1,3, Melissa Hwang2, Saurabh Vashsishtha2, Zachary M Barnes1, 3 , Nancy G Klimas3, 4, Mary Ann Fletcher1,3, Gordon Broderick2,3
Affiliations: 1 Department of Medicine, University of Miami, Miami, FL, USA
2 Department of Medicine, University of Alberta, Edmonton, AB, Canada
3 Institute for Neuro Immune Medicine, Nova Southeastern University, Fort Lauderdale, FL, USA
4Miami Veterans Affairs Healthcare System, Miami, FL, USA
Abstract: Objectives. While biomarkers for myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) are emerging, the mechanisms driving symptom severity remain poorly understood. We hypothesize that sex hormones and their mediation immune function may play a role. Our objective was to identify co-expression of cytokines and sex hormones that also coincide with changes in ME/CFS severity. Methods. As part of an ongoing study, blood samples were collected, at rest, from n=18 female ME/CFS subjects, who were 35-73 years of age. Illness severity was characterized using standard self-assessment instruments that included the multi-dimensional fatigue index (MFI), Beck Depression Index (BDI), and the short form 36 (SF-36). Blood samples were analyzed for concentrations of estradiol and progesterone, as well as for 16 cytokines, using a chemiluminescent assay. Concentrations were log2 transformed and z scaled. Associations between symptoms and blood-borne markers were estimated, based on partial correlation, and adjusted for age and body mass index (BMI). Null probability estimates were based on an asymptotic normal distribution and adjusted for false discovery using Benjamini Hochberg criteria. Results. Analysis revealed direct and significant correlations (adjusted p<0.05) linking SF-36 measures for physical limit, emotional limit, and pain, with changes in progesterone (r=0.66), IL-4 (r=-0.71) and IL-1a (r=-0.76), respectively. The MFI measure for mental fatigue correlated positively with changes in IL-2 (r=0.62), while reduced motivation score correlated negatively with the interaction of progesterone and IL-17 (r=-0.63). In each case, symptoms correlating with blood-borne markers were directly part of a larger symptom cluster. Conclusion. These preliminary results suggest that aspects of mental, emotional, and physical fatigue, including pain, correlate significantly with levels of progesterone, with that of specific Th1, Th2, and Th17, and with inflammatory cytokines. Importantly, the severity of a major symptom cluster may be driven by endocrine mediation of Th17 activity in ME/CFS.
Title: Th17 as a Potential Probiotic Therapeutic Target in Inflammatory Bowel Diseases
Authors: Eddy Owagaa and Jung-Su Changb,＊
Affiliations: a Institute of Food and Bioresources Technology, Dedan Kimathi University of Technology, Nyeri, Kenya. b School of Nutrition and Health Sciences, College of Public Health and Nutrition, Taipei Medical University, Taipei, Taiwan. R.O.C. ＊ To whom correspondence should be addressed. E-mail: email@example.com; School of Nutrition and Health Sciences, College of Public Health and Nutrition,Taipei Medical University, Taipei, Taiwan, 250 Wu-Xing Street, Taipei 110, Taiwan, R.O.C; Tel.:+886-(2)27361661#6542, Fax:+886-(2)2737-3112
Abstract: Inflammatory Bowel Diseases (IBD) are characterized by wasting and chronic intestinal inflammation. These symptoms are triggered by various cytokine-mediated pathways. In recent years, it has been shown that Th17 cells play a central role in the pathogenesis of IBD. Thus, Th17 cells are attractive therapeutic targets. Th17 cells preferentially produce IL-17, IL-17F, and IL-22 as signature cytokines. The role of the interplay between host genetics and intestinal microbiota in the pathogenesis of IBD has been demonstrated. Probiotics are live microorganisms that, when orally ingested in adequate amounts, confer a health benefit on the host by modulating enteric flora or by stimulating the local immune system. Several studies indicate the effectiveness of probiotics in the treatment of IBD (ulcerative colitis, pouchitis, and Crohn's disease). There is mounting evidence of probiotics selectively targeting the Th17 cell lineage during the the management of inflammatory and autoimmune diseases. This review highlights the critical role of Th17 cells in the pathogenesis of IBD and the rationale for using probiotics as novel therapeutic approaches in treating IBD through the manipulation of Th17 cells.
Keywords: Th17; probiotics; Inflammatory Bowel Diseases; inflammation
Title: Scanning for Therapeutic Targets within the Cytokine Network of Idiopathic Inflammatory Myopathies
Authors: Boel De Paepe1, Jana Zschüntzsch2
Affiliations: 1Neuromuscular Reference Center, Laboratory for Neuropathology, Ghent University Hospital, Belgium 2Clinic for Neurology, University Medical Centre, Göttingen University, Germany
Abstract: Idiopathic inflammatory myopathies (IIM) constitute a heterogeneous group of chronic disorders that includes dermatomyositis (DM), polymyositis (PM), sporadic inclusion body myositis (IBM), and necrotizing autoimmune myopathy (NAM). They represent distinct pathological entities but, most often, share the predominant symptom of inflammation in muscle tissue. Many of the immunopathogenic processes behind IIM remain poorly understood, but the crucial role played by cytokines as essential regulators of the intramuscular build-up of inflammation is undisputed. This review describes the extensive cytokine network inside IIM muscle. Patient tissues are characterized by the strong expression of subsets of Tumor Necrosis Factors (TNFa, LTb, BAFF), Interferons (IFNa/b/g), Interleukins (IL-1/6/12/15/18/23), and Chemokines (CXCL9/10/11/13, CCL2/3/4/8/19/21). Exploration of potential, disease modifying agents, based on the manipulation of the cytokine network, is provided. Reported responses to anti-TNFa treatment in IIM are conflicting, and the new onset of DM/PM has been described after administration of anti-TNFa agents for the treatment of other diseases. These studies point to the complex effects of TNFa neutralization. Treatment with the anti-IFNα monoclonal antibody has been shown to suppress the IFN type 1 gene signature in DM/PM patients and improve muscle strength. Beneficial effects of anti-IL-1 and anti-IL-6 therapy have also been reported. Understanding the interplay of cytokines in IIM will not only guide the development of therapeutic strategies, but might also inspire approaches for subtype patients and predict treatment outcomes.
Title: New Immunosuppressive Therapies in the Treatment of Uveitis
Authors: Salvador Mérida, Elena Palacios, Navea Amparo and Francisco Bosch Morell
Abstract: Uveitis is an inflammatory process that initially starts in the uvea, and can also affect other adjacent eye structures. It is currently the fourth leading cause of blindness in developed countries. Corticoids are probably the most widespread treatment, but resorting to other immunosuppressive treatments is a frequently necessary practice. Since the implication of different cytokines in uveitis has been well demonstrated, the majority of recent treatments against this disease include inhibitors or antibodies that act against these cytokines. Nevertheless, adequately treating each uveitis type entails a difficult therapeutic decision because no clear recommendations are found in the literature, given the dearth of protocolized clinical assays and case-control studies. This review aims to present the mechanisms and main indications of the most modern immunosuppressive drugs affecting cytokines.