Together with an international research team, Andreas Koeberle has shown that a natural substance from the sea can modulate inflammatory processes. The scientists synthesised the substance cyclosmenospongin, which had previously been discovered in a sponge of the genus Spongia native to Australia. In the laboratory, they found that the active compound comprehensively alters the lipid profile of human immune cells. “The compounds studied reduced the production of pro-inflammatory leukotrienes whilst simultaneously increasing the levels of several messenger substances associated with the suppression and resolution of inflammation. They therefore significantly alter the metabolic programme of immune cells,” explains Koeberle.
Reprogramming rather than blocking inflammation
The researchers were particularly surprised to find that this effect is closely linked to the storage of fats in immune cells. Cyclosmenospongin reduces the levels of neutral lipids, triglycerides and cholesterol esters. “As a result, the cells had less material available to produce pro-inflammatory signalling molecules. We achieved similar effects when we specifically inhibited enzymes involved in lipid storage. This demonstrates a close link between fat accumulation in immune cells and inflammation, which was previously unknown in this form,” says Koeberle.
The research findings provide new avenues for better controlling excessive or chronic inflammation. Colleagues at the University of Innsbruck laid the chemical foundations for the study by synthesising and modifying variants of the natural compounds. The biological investigations were carried out in Graz and Naples, amongst other locations.
Publication:
Waltl, L., Holubek, D., Speck, K., Wildermuth, R., Haut, F.-L., Permann, S., Plangger, I., Steinborn, C., Rao, Z., D’Avino, D., Cerqua, I., Stadler, J., Roviezzo, F., Schlenke, P., Siller, A., Schennach, H., Koeberle, S.C., Pferschy-Wenzig, E.-M., Rossi, A., Magauer, T., Koeberle, A. Reorganisation of innate immune cell lipid profiles by bioinspired meroterpenoids to limit inflammation. Advanced Science, August 18, 2026, DOI: https://doi.org/10.1002/advs.76861