FEB 27, 2019 06:07 PM PST

Anti-Inflammatory Meds without Side Effects, Please

Drugs such as ibuprofen or aspirin that relieve pain and lower fever are among the most frequently used drugs worldwide. These medicines aid in mitigating inflammation. 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 signaling substances in immune cells during an inflammatory reaction. 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 period 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 analyzed.

The distinctive feature of the methodology developed in Jena is its sensitivity: the inflammation-resolving substances of the second phase are useful in concentrations about 1,000 times lower than the inflammatory signal substances of the first inflammatory phase. Very sensitive analytics is required 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.

Sources: Science Daily, FASEB, YouTube

About the Author
You May Also Like
DEC 19, 2018
Immunology
DEC 19, 2018
Breast Cancer - Immunotherapy's Nemesis
Researchers find that breast cancer can evade immunotherapy...
DEC 21, 2018
Microbiology
DEC 21, 2018
How the Gut Microbiome Controls the Intestinal Immune System
The gut microbiome has many important functions, including helping us digest food. But it has to protect itself from the immune system....
JAN 09, 2019
Immunology
JAN 09, 2019
What We Don't Know Won't Hurt Us, Right?
A review in Frontiers in Pediatrics describes a common food additive that could both create and trigger autoimmune attacks, calling for warnings on food labels pending further tests....
MAR 17, 2019
Microbiology
MAR 17, 2019
In Space, Dormant Viruses Can Reactivate
Some astronauts have lived onboard the International Space Station for hundreds of days. Researchers are learning more about the things that can happen in that time....
APR 02, 2019
Cancer
APR 02, 2019
Widely Prescribed Breast Cancer Medication Promotes Metastasis
The primary goals of metastatic breast cancer treatment are to ensure that the patient has the longest survival possible while experiencing the highes...
APR 11, 2019
Health & Medicine
APR 11, 2019
Drug-resistant Candida Auris is Spreading
A drug-resistant fungal yeast, Candida auris, is spreading throughout hospitals worldwide. Deemed “an urgent threat” by the Center for Disease...
Loading Comments...