Studies on in vitro models of cellular immunity: The role of T and B cells in the secretion of lymphotoxin

When normal murine spleen cells were treated with anti-theta serum and complement, they failed to produce LT or synthesize cellular DNA when stimulated in vitro with PHA. Theta-positive cells were responsible for LT production in spleens removed from X-irradiated and bone marrow- or thymus-reconstituted animals. Finally, spleens from congenitally athymic Nu/Nu mice failed to produce LT when stimulated with pokeweed mitogen or phytohemagglutinin. © 1973

Intra-articular vs. systemic administration of etanercept in antigen-induced arthritis in the temporomandibular point. Part I: histological effects

<p>Abstract</p> <p>Background</p> <p>Temporomandibular joint (TMJ) arthritis in children causes alterations in craniomandibular growth. This abnormal growth may be prevented by an early anti-inflammatory intervention. We have previously shown that intra-articular (IA) corticosteroid reduces TMJ inflammation, but causes concurrent mandibular growth inhibition in young rabbits. Blockage of TNF-α has already proven its efficacy in children with juvenile idiopathic arthritis not responding to standard therapy. In this paper we evaluate the effect of IA etanercept compared to subcutaneous etanercept in antigen-induced TMJ-arthritis in rabbits on histological changes using histomorphometry and stereology. This article presents the data and discussion on the anti-inflammatory effects of systemic and IA etanercept. In Part II the data on the effects of systemic and IA etanercept on facial growth are presented.</p> <p>Methods</p> <p>Forty-two rabbits (10 weeks old) pre-sensitized with ovalbumin and locally induced inflammation in the temporomandibular joints were divided into three groups: a placebo group receiving IA saline injections in both joints one week after arthritis induction (n = 14), an IA etanercept group receiving 0.1 mg/kg etanercept per joint one week after arthritis induction (n = 14) and a systemic etanercept group receiving 0.8 mg/kg etanercept weekly throughout the 12-week study (n = 14). Arthritis was maintained by giving four inductions three weeks apart. Additional IA saline or etanercept injections were also given one week after the re-inductions. Histomorphometric and unbiased stereological methods (optical fractionator) were used to assess and estimate the inflammation in the joints.</p> <p>Results</p> <p>The histomorphometry showed synovial proliferation in all groups. The plasma cell count obtained by the optical fractionator was significantly reduced when treating with systemic etanercept but not with IA etanercept. Semi-quantitative assessments of synovial proliferation and subsynovial inflammation also showed reduced inflammation in the systemic etanercept group. However, the thickness of the synovial lining and volume of the subsynovial connective tissue showed no differences between the groups.</p> <p>Conclusion</p> <p>An anti-inflammatory effect of systemic etanercept on the synovial tissues in the temporomandibular joint was shown. However, IA etanercept at the given dose had no significant effect on the severity of chronic inflammation on the parameters here tested in ovalbumin antigen-induced arthritis.</p

Large animal models of cardiovascular disease

The human cardiovascular system is a complex arrangement of specialized structures with distinct functions. The molecular landscape, including the genome, transcriptome and proteome, is pivotal to the biological complexity of both normal and abnormal mammalian processes. Despite our advancing knowledge and understanding of cardiovascular disease (CVD) through the principal use of rodent models, this continues to be an increasing issue in today's world. For instance, as the ageing population increases, so does the incidence of heart valve dysfunction. This may be because of changes in molecular composition and structure of the extracellular matrix, or from the pathological process of vascular calcification in which bone-formation related factors cause ectopic mineralization. However, significant differences between mice and men exist in terms of cardiovascular anatomy, physiology and pathology. In contrast, large animal models can show considerably greater similarity to humans. Furthermore, precise and efficient genome editing techniques enable the generation of tailored models for translational research. These novel systems provide a huge potential for large animal models to investigate the regulatory factors and molecular pathways that contribute to CVD in vivo. In turn, this will help bridge the gap between basic science and clinical applications by facilitating the refinement of therapies for cardiovascular disease. Copyright (c) 2016 John Wiley & Sons, Ltd

Inflammatory resolution: New opportunities for drug discovery

Treatment of inflammatory diseases today is largely based on interrupting the synthesis or action of mediators that drive the host’s response to injury. Non-steroidal anti-inflammatories, steroids and antihistamines, for instance, were developed on this basis. Although such small-molecule inhibitors have provided the main treatment for inflammatory arthropathies and asthma, they are not without their shortcomings. This review offers an alternative approach to the development of novel therapeutics based on the endogenous mediators and mechanisms that switch off acute inflammation and bring about its resolution. It is thought that this strategy will open up new avenues for the future management of inflammation-based diseases