April 6, 2018
Keio University School of Medicine
A research group led by Senior Lecturer Makoto Ishii and Collaborative Researcher Nam-gung Hu of Professor Tomoko Betsuyaku's laboratory at the Department of Internal Medicine (Pulmonology), and Professor Naoki Hasegawa of the Center for Infectious Diseases and Infection Control, both at the Keio University School of Medicine, has unraveled a new mechanism behind the protective effects of macrolide antibiotics—commonly used oral antibiotics—that modulate the immune system and suppress inflammation, separate from their antibacterial action.
In Japan, macrolides are the most frequently prescribed antibiotics, accounting for 33% of all oral antibiotic use (according to 2013 statistics from the Ministry of Health, Labour and Welfare). In addition to their antibacterial action of killing or inhibiting the growth of bacteria, macrolides are known to have immunomodulatory and anti-inflammatory effects. Due to these expected effects, they are widely used in clinical practice as a therapeutic agent for many respiratory diseases, such as preventing exacerbations of bronchiectasis, diffuse panbronchiolitis, and chronic obstructive pulmonary disease (COPD). However, the detailed mechanism behind these effects has remained unclear until now.
The research group led by Senior Lecturer Makoto Ishii has now discovered that the administration of clarithromycin, a macrolide antibiotic, increases the number of CD11b-positive Gr-1-positive cells (MDSC-like cells), which have properties similar to myeloid-derived suppressor cells (MDSCs), by approximately 2.5 to 3.3 times in the lungs and spleen. Furthermore, using mouse models (an endotoxin shock model induced by bacterial components and a secondary bacterial pneumonia model following influenza infection), they clarified that these increased MDSC-like cells play a major role in the immunomodulatory effects. The study also suggests the possibility that the administration of clarithromycin increases MDSC-like cells in humans as well.
Since the inappropriate use of antibiotics leads to the emergence of drug-resistant bacteria, the Ministry of Health, Labour and Welfare is promoting a reduction in antibiotic consumption. The findings of this research are expected to contribute to the development of new drugs that specifically target the immunomodulatory effects of macrolides. This is significant from the perspective of combating antimicrobial resistance (AMR), a global challenge.
The results of this research were published in the online edition of the international scientific journal "PLOS Pathogens" on April 5, 2018 (US Eastern Time).
Please see below for the full press release.