Christina Weigert

Interleukin 4 as a potential drug candidate for psoriasis

Background: Interleukin 4 (IL-4) is the central cytokine driving the differentiation of naive CD4+ T helper (TH) cells into anti-inflammatory IL-4-producing TH2 cells. In contrast, IL-12/IL-23 promotes the development of TH1/TH17 immune responses that induce organ-specific autoimmune diseases such as psoriasis or multiple sclerosis. Objective: We focus on the potential of IL-4 and TH2 induction to treat inflammatory autoimmune diseases. Methods: Here, we summarize the basics for the establishment of the in vitro and in vivo conditions for the generation of TH2 immune responses, followed by various experimental data showing the therapeutic use of IL-4 for the therapy of autoimmune diseases. This data and early experiences with recombinant human IL-4 (rhIL-4) in the therapy of patients with cancer set the basis for the clinical introduction of rhIL-4 in the treatment of patients with psoriasis in a Phase I/II trial. Conclusion: IL-4 seems to act by inducing an anti-inflammatory phenotype and further clinical trials will explore the promising therapeutic potency of IL-4 in psoriasis during the upcoming era of biologics.

Co-transfection of messenger RNA and siRNA as a method to study the efficiency of siRNA.

The definition of an optimal siRNA results from the in vitro testing of several siRNA designed to specifically target a gene. Usually, such in vitro tests consist in the transfection of the several siRNA duplexes in a cell expressing stably the gene of interest. When a siRNA specific for a mRNA coding toxic proteins (certain transcription factors, transporters, toxins, cell cycle controlling proteins, etc.) must be tested, the generation of a target cell is difficult. Here we report a quick method to test the efficiency of a siRNA through its co-transfection with the targeted mRNA. This technique can be used as a fast method to test siRNA even when they target genes that cannot be stably expressed in the cells of interest. *Both authors contributed equally to the work. This work was supported by “Förderprogramm Biotechnologie,” a grant from the government of Baden Württemberg, Germany and by a “IZKF-Verbundprojekt,” a grant from the University of Tübingen. JP is supported by the DFG: Graduiertenkolleg “Infektionsbiologie” in Tübingen and JPC is supported by a “Fortüne” grant from the University of Tübingen.

Biologics bei entzündlichen Krankheiten der Haut: Wirkungsmechanismen — Möglichkeiten — Risiken

Mitte der 80er Jahre begann die Einfuhrung der Biologics in die Medizin. Zu den ersten Biologics, die insbesondere auch in der Dermatologie untersucht wurden, zahlen das Interleukin 2 (IL-2) [40] und die Interferone (IFN), ursprunglich zur Behandlung viraler Krankheiten und entzundlicher Krankheiten wie der Psoriasis gedacht [20]. In den 90er Jahren hat sich das Spektrum der zur Verfugung stehenden Biologics deutlich erweitert und der Terminus Biologics eingeburgert. Heute wird hierunter eine grose Gruppe von Medikamenten verstanden, deren gemeinsames Merkmal ist, dass sie entweder naturlichen Glykoproteinen entsprechen, wie IL-2, IFN-α und Antikorpern, oder pharmakologisch modifizierten (pegyliertes IFN-α) oder molekular modifizierten Molekulen, wie Etanercept und Infliximab (Tabelle 1). Diese Modifikationen wurden entweder durchgefuhrt, um die Halbwertszeit und somit die Bioverfugbarkeit zu erhohen (Etanercept) oder um ein Molekul, das ursprunglich nicht vom Menschen stammt, so zu humanisieren, dass es vom Immunsystem des Menschen nicht mehr als fremd erkannt wird (Infliximab).