Jena University pharmacists and international partners present highly sensitive test system for anti-inflammatory drugs
An international research team led by Friedrich Schiller University in Jena has developed a highly sensitive cell model to study the complex effects – and side effects – of anti-inflammatory drugs, with the ultimate aim of preventing chronic inflammation.
Drugs such as ibuprofen or aspirin that relieve pain and lower fever are among the most frequently used drugs worldwide. They are used above all for the treatment of inflammatory reactions.
However, in spite of their indisputable effectiveness and frequent use, we do not yet fully understand the underlying mechanisms of these drugs. In addition, when these drugs are taken, serious side effects occur and again, the causes of which have also not been sufficiently clarified.
The research team led by pharmacists Dr Jana Gerstmeier and Prof. Oliver Werz of the University of Jena has developed a cell model with which they can find answers to these questions.
As the team’s scientists report in the specialist publication, ‘The FASEB Journal’, they have succeeded in clarifying the complex effect of active compounds that are administered on the formation of endogenous signalling substances in immune cells during an inflammatory reaction (DOI: 10.1096/fj.201802509R).
In the future, this will make it possible to develop new active drugs with fewer side effects. Working groups from Harvard Medical School in Boston and the Karolinska Institute in Stockholm were also involved in the research work.
Inflammation occurs in two phases
“Inflammation proceeds – roughly speaking – in two successive phases,” explains Markus Werner, a doctoral student at the Chair of Pharmaceutical and Medical Chemistry of Jena University and first author of the study. During the initial phase, type ‘M1’ immune cells (macrophages) are active. They produce inflammatory messenger substances (prostaglandins and leukotrienes) from unsaturated fatty acids, which trigger typical symptoms such as fever and pain.
After a few days, the second phase begins, in which the inflammation is resolved. In this phase, type ‘M2’ macrophages are active, which produce inflammation-resolving messenger substances from the fatty acids (called resolvins).
“Conventional drugs intervene equally in both phases,” says Dr Jana Gerstmeier. “They reduce the production of both proinflammatory messenger substances and inflammation-resolving mediators.” This alleviates the first acute inflammatory reaction, but at the same time it also hampers the second phase in which the inflammation resolves. “There is a risk of inflammation not being stopped and continuing to progress, so that secondary diseases occur.” Ideally, drugs should therefore reduce only the acute phase, but not impair the phase in which the inflammation resolves.
The special feature of the methodology is its sensitivity
The newly developed cell model enables researchers to investigate the efficacy of drugs in both inflammatory phases. “For this purpose, we use human immune cells (M1 and M2), which we pre-treat with the drug to be tested before inducing an inflammatory reaction using pathogenic bacteria,” explains Jana Gerstmeier. The messenger substances released by the cells are analysed.
The special feature of the methodology developed in Jena is its sensitivity: the inflammation-resolving substances of the second phase are effective in concentrations about 1,000 times lower than the inflammatory signal substances of the first inflammatory phase. Very sensitive analytics are required in order to be able to detect these substances, and the Jena laboratory is one of the few laboratories in the world to have mastered this methodology. Using a mass spectrometer, several dozen mediator molecules that have been released are detected and an individual spectrum is created for each active ingredient. This allows conclusions to be drawn about the influence of the drug on the entire inflammatory process.
Dr Jana Gerstmeier
Institute of Pharmacy of Friedrich Schiller University, Jena
Philosophenweg 14, 07743 Jena, Germany
Tel.: +49 (0)3641 / 949801
Werner M, Targeting biosynthetic networks of the proinflammatory and proresolving lipid metabolome, FASEB J. 33, 000–000 (2019), DOI: 10.1096/fj.201802509R, https://www.fasebj.org/doi/pdf/10.1096/fj.201802509R
Dr. Ute Schönfelder | idw - Informationsdienst Wissenschaft
To proliferate or not to proliferate
21.03.2019 | Max-Planck-Institut für molekulare Zellbiologie und Genetik
Discovery of a Primordial Metabolism in Microbes
21.03.2019 | Leibniz-Institut DSMZ-Deutsche Sammlung von Mikroorganismen und Zellkulturen GmbH
Nano- and microtechnology are promising candidates not only for medical applications such as drug delivery but also for the creation of little robots or flexible integrated sensors. Scientists from the Max Planck Institute for Polymer Research (MPI-P) have created magnetic microparticles, with a newly developed method, that could pave the way for building micro-motors or guiding drugs in the human body to a target, like a tumor. The preparation of such structures as well as their remote-control can be regulated using magnetic fields and therefore can find application in an array of domains.
The magnetic properties of a material control how this material responds to the presence of a magnetic field. Iron oxide is the main component of rust but also...
Due to the special arrangement of its molecules, a new coating made of corn starch is able to repair small scratches by itself through heat: The cross-linking via ring-shaped molecules makes the material mobile, so that it compensates for the scratches and these disappear again.
Superficial micro-scratches on the car body or on other high-gloss surfaces are harmless, but annoying. Especially in the luxury segment such surfaces are...
The Potsdam Echelle Polarimetric and Spectroscopic Instrument (PEPSI) at the Large Binocular Telescope (LBT) in Arizona released its first image of the surface magnetic field of another star. In a paper in the European journal Astronomy & Astrophysics, the PEPSI team presents a Zeeman- Doppler-Image of the surface of the magnetically active star II Pegasi.
A special technique allows astronomers to resolve the surfaces of faraway stars. Those are otherwise only seen as point sources, even in the largest telescopes...
Researchers at Chalmers University of Technology and the University of Gothenburg, Sweden, have proposed a way to create a completely new source of radiation. Ultra-intense light pulses consist of the motion of a single wave and can be described as a tsunami of light. The strong wave can be used to study interactions between matter and light in a unique way. Their research is now published in the scientific journal Physical Review Letters.
"This source of radiation lets us look at reality through a new angle - it is like twisting a mirror and discovering something completely different," says...
New research group at the University of Jena combines theory and experiment to demonstrate for the first time certain physical processes in a quantum vacuum
For most people, a vacuum is an empty space. Quantum physics, on the other hand, assumes that even in this lowest-energy state, particles and antiparticles...
11.03.2019 | Event News
01.03.2019 | Event News
28.02.2019 | Event News
21.03.2019 | Life Sciences
21.03.2019 | Physics and Astronomy
21.03.2019 | HANNOVER MESSE