Researchers develop a highly sensitive cellular model to study the complex effects of anti-inflammatory drugs

Pharmacists from the University of Jena and their international partners present a highly sensitive test system for anti-inflammatory drugs

Medications such as ibuprofen or aspirin, which relieve pain and reduce fever, are among the most frequently used drugs in the world. They are mainly used for the treatment of inflammatory reactions. However, despite their indisputable efficacy and frequent use, we still do not fully understand the underlying mechanisms of these drugs. In addition, when taking these drugs, serious side effects occur and, again, whose causes have not been sufficiently clarified.

The research team led by pharmacists Jana Gerstmeier and Oliver Werz of the University of Jena has developed a cellular model to find answers to these questions. As reported by the scientists of the team in the specialized publication & # 39;The FASEB newspaper& # 39;, they were able to clarify the complex effect of active compounds administered on the formation of endogenous signaling substances in immune cells during an inflammatory reaction (DOI: 10.1096 / fj.201802509R). In the future, this will help develop new active drugs with fewer side effects. Working groups from Harvard Medical School in Boston and the Karolinska Institute in Stockholm also participated in the research.

The inflammation occurs in two phases

"Inflammation continues – roughly – in two successive phases," says Markus Werner, a doctoral student at the chair of pharmaceutical and medical chemistry at the University of Jena and the first author of the study. During the initial phase, the immune cells of the type 'M1 & # 39; (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 and produce messenger substances that resolve inflammation from fatty acids (called resolvin).

"Conventional drugs intervene equally in both phases," says Dr. Jana Gerstmeier. "They reduce the production of pro-inflammatory messenger substances and mediators of resolution of inflammation." This attenuates the first acute inflammatory reaction, but also hinders the second phase of resolution of inflammation. "There is a risk that inflammation will not be stopped and continues to progress, resulting in the appearance of secondary diseases." Ideally, medications should only reduce the acute phase, but not the phase of resolution of inflammation.

The peculiarity of the methodology is its sensitivity

The newly developed cellular model allows researchers to study the efficacy of drugs in both inflammatory phases. "For this, we use human immune cells (M1 and M2), which we pre-treat with the drug to test before causing an inflammatory reaction with the help of pathogenic bacteria," explains Jana Gerstmeier. The messenger substances released by the cells are badyzed.

The methodology developed at Jena is characterized by its sensitivity: the second-phase substances that resolve inflammation are effective at concentrations about 1,000 times lower than the inflammatory signal substances of the first inflammatory phase. Very sensitive badyzes are needed to detect these substances, and the Jena laboratory is one of the few laboratories in the world to master this methodology. With the aid of a mbad spectrometer, several tens of mediator molecules 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.