The impact of biologic agents on health-related quality of life outcomes in patients with psoriasis

Introduction: Psoriasis is a common, immune-mediated skin disease often associated with significant physical and psychosocial impairment. Antipsoriatic biologic agents offer patients unparalleled treatment potential in regard to greater skin clearance and overall improved quality of life. Evaluation of the therapeutic efficacy of biologic agents on the full psoriasis disease burden must account for their impact on both physical symptoms, as well as patient-reported, health-related quality of life (HRQoL) measurements.

Areas covered: Results from numerous clinical trials demonstrate the significant clinical efficacy of biological agents targeting tumor necrosis factor-α (TNF-α) and the interleukin (IL)-12/23 and IL-17 immune pathways. However, relatively limited data is available evaluating their full effect on quality of life outcomes. This review will discuss the most relevant and up-to-date clinical data on HRQoL measurements related to treatment with these aforementioned biologic agents.

Expert commentary: Patient-reported outcomes (i.e. Dermatology Life Quality Index) are being used with increasing frequency in clinical trials, and provide valuable information on the impact of psoriasis on numerous aspects of day-to-day living. These outcomes must also be incorporated in clinical practice, in addition to physical assessment of disease severity, treatment decisions, and therapeutic response in the psoriasis patient population.     

Th1/Th2类细胞因子失衡和一氧化氮合酶在内毒素休克性肺损伤中的作用机制

目的　观察内毒素 (LPS)诱导的急性肺损伤 (ALI)大鼠血Th1/Th2类细胞因子浓度以及肺组织一氧化氮合酶 (NOS)活性和NOS基因表达 ,以探讨它们在ALI中的发病机制。方法　采用颈静脉注入LPS复制大鼠急性肺损伤模型 ,用ELISA法检测其外周血单个核细胞产生IFN -γ、IL - 4水平及IFN -γ/IL - 4比值 ;用放射免疫 (RIA)的方法测定LPS注射后大鼠肺组织NOS活性 ;采用逆转录聚合酶链反应 (RT -PCR)检测LPS注射大鼠肺组织内源型一氧化氮合酶 (eNOS)、诱导型一氧化氮合酶 (iNOS)mRNA表达情况。结果　与正常对照组相比 ,急性肺损伤组外周血PBMC产生IFN -γ水平、IFN -γ/IL - 4比值明显升高 (P <0 0 5 ,P <0 0 0 1) ,而IL - 4水平差异无显著性 (P >0 0 5 ) ,同时伴随NOS活性 [( 0 30± 0 0 5 )U/mgpro]明显高于对照组 [( 0 2 4± 0 0 3) ,P <0 0 5 ]。iNOSmRNA表达( 0 70± 0 2 0 )显著高于对照组 (P <0 0 5 ) ,eNOSmRNA表达未见明显变化 (P >0 0 5 )。肺组织病理切片显示大鼠发生ALI。结论　LPS休克肺损伤时 ,体内存在Th1/Th2类细胞因子水平失衡 ,同时伴有NOS活性增高 ,而NOS的主要来源为iNOS基因表达增强     

Metabolic regulation of innate and adaptive lymphocyte effector responses

Innate and adaptive lymphocytes employ diverse effector programs that provide optimal immunity to pathogens and orchestrate tissue homeostasis, or conversely can become dysregulated to drive progression of chronic inflammatory diseases. Emerging evidence suggests that CD4⁺ T helper cell subsets and their innate counterparts, the innate lymphoid cell family, accomplish these complex biological roles by selectively programming their cellular metabolism in order to instruct distinct modules of lymphocyte differentiation, proliferation, and cytokine production. Further, these metabolic pathways are significantly influenced by tissue microenvironments and disease states. Here, we summarize our current knowledge on how cell-intrinsic metabolic factors modulate the context-dependent bioenergetic pathways that govern innate and adaptive lymphocytes. Further, we propose that a greater understanding of these pathways may lead to the identification of unique features in each population and provoke the development of novel therapeutic strategies to modulate lymphocytes in health and disease.     

Larval Echinococcus multilocularis infection reduces dextran sulphate sodium‐induced colitis in mice by attenuating T helper type 1/type 17‐mediated immune reactions

The tumour‐like growth of larval Echinococcus multilocularis tissue (causing alveolar echinococcosis, AE) is directly linked to the nature/orientation of the periparasitic host immune‐mediated processes. Parasite‐mediated immune suppression is a hallmark triggering infection outcome in both chronic human and murine AE. So far, little is known about secondary systemic immune effects of this pathogen on other concomitant diseases, e.g. endogenous gut inflammation. We examined the influence of E. multilocularis infection on murine dextran sodium sulphate (DSS) ‐induced colitis. At 3 months after E. multilocularis infection (chronic stage), the mice were challenged with 3% DSS in the drinking water for 5 days plus subsequently with tap water (alone) for another 4 days. After necropsy, fixed tissues/organs were sectioned and stained with haematoxylin & eosin for assessing inflammatory reactions. Cytokine levels were measured by flow cytometry and quantitative RT‐PCR. Colitis severity was assessed (by board‐certified veterinary pathologists) regarding (i) colon length, (ii) weight loss and (iii) a semi‐quantitative score of morphological changes. The histopathological analysis of the colon showed a significant reduction of DSS‐induced gut inflammation by concomitant E. multilocularis infection, which correlated with down‐regulation of T helper type 1 (Th1)/Th17 T‐cell responses in the colon tissue. Echinococcus multilocularis infection markedly reduced the severity of DSS‐induced gut inflammation upon down‐regulation of Th1/Th17 cytokine expression and attenuation of CD11b⁺ cell activation. In conclusion, E. multilocularis infection remarkably reduces DSS‐induced colitis in mice by attenuating Th1/Th17‐mediated immune reactions.     

Combined therapies to treat complex diseases: The role of the gut microbiota in multiple sclerosis

The commensal microbiota has emerged as an environmental risk factor for multiple sclerosis (MS). Studies in experimental autoimmune encephalomyelitis (EAE) models have shown that the commensal microbiota is an essential player in triggering autoimmune demyelination. Likewise, the commensal microbiota modulates the host immune system, alters the integrity and function of biological barriers and has a direct effect on several types of central nervous system (CNS)-resident cells. Moreover, a characteristic gut dysbiosis has been recognized as a consistent feature during the clinical course of MS, and the MS-related microbiota is gradually being elucidated. This review highlights animal studies in which commensal microbiota modulation was tested in EAE, as well as the mechanisms of action and influence of the commensal microbiota not only in the local milieu but also in the innate and adaptive immune system and the CNS. Regarding human research, this review focuses on studies that show how the commensal microbiota might act as a pathogenic environmental risk factor by directing immune responses towards characteristic pathogenic profiles of MS. We speculate how specific microbiome signatures could be obtained and used as potential pathogenic events and biomarkers for the clinical course of MS. Finally, we review recently published and ongoing clinical trials in MS patients regarding the immunomodulatory properties exerted by some microorganisms. Because MS is a complex disease with a large variety of associated environmental risk factors, we suggest that current treatments combined with strategies that modulate the commensal microbiota would constitute a broader immunotherapeutic approach and improve the clinical outcome for MS patients.