gms | German Medical Science

11th Malaria Meeting

Malaria Group / Section Antiparasitic Chemotherapy of the Paul-Ehrlich-Society (PEG e. V.) in cooperation with the German Society for Tropical Medicine and International Health (DTG e. V.) and the German Society for Parasitology (DGP e. V.)

08.11. - 09.11.2013, Aachen

Doxycycline inhibits experimental cerebral malaria by altering T cell responses and reducing inflammatory and tissue-degrading mediators

Meeting Abstract

  • Kim E. Schmidt - Institute of Medical Microbiology, Immunology and Parasitology, University Hospital Bonn, Bonn, Germany
  • Janina M. Küpper - Institute of Medical Microbiology, Immunology and Parasitology, University Hospital Bonn, Bonn, Germany
  • Judith Alferink - Department of Psychiatry and Psychotherapy, University Hospital Muenster, Muenster, Germany; Institute of Molecular Psychiatry, University Hospital Bonn, Bonn, Germany
  • Beatrix Schumak - Institute of Medical Microbiology, Immunology and Parasitology, University Hospital Bonn, Bonn, Germany
  • Andreas Limmer - Department of Orthopaedics, University Hospital Bonn, Bonn, Germany; Institutes of Molecular Medicine and Experimental Immunology, University Hospital Bonn, Bonn, Germany
  • Sabine Specht - Institute of Medical Microbiology, Immunology and Parasitology, University Hospital Bonn, Bonn, Germany
  • Achim Hörauf - Institute of Medical Microbiology, Immunology and Parasitology, University Hospital Bonn, Bonn, Germany

11th Malaria Meeting. Aachen, 08.-09.11.2013. Düsseldorf: German Medical Science GMS Publishing House; 2014. Doc13mal05

doi: 10.3205/13mal05, urn:nbn:de:0183-13mal055

Published: January 29, 2014

© 2014 Schmidt et al.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by-nc-nd/3.0/deed.en). You are free: to Share – to copy, distribute and transmit the work, provided the original author and source are credited.


Outline

Text

We investigated the impact of doxycycline treatment on Plasmodium berghei ANKA (PbA) induced experimental cerebral malaria (ECM). The complex inflammatory networks triggerd by the parasite leads to the destruction of the blood brain barrier (BBB). Administration of doxycycline prevented neuropathology in PbA infected mice. Local inflammation was reduced to a minimum and BBB damage was prevented.

Other tetracyclie derivatives show similar protective effects, but only those with known immune-regulatory properties.

Our results provide evidence that the inhibition of ECM is to a large extend by anti-inflammatory actions of doxycycline, despite observed anti-parasitic effects. Protection is observed in high dose infected animals and likewise in animals receiving additional parasites later infection.

Analysing brain tissue by RNA-array and on protein levels, we found that in treated animals, the expression of CCL5, an important T cell recruitment factor in inflammation was reduced. Accordingly, T cell infiltration was impaired. The T cells accumulated in the spleen and despite similar activation compared to PbA infected controls, these cells showed reduced parasite-specific cytotoxicity after doxycycline treatment. In addition, ECM development could be associated with increased expression and activity of gelatinolytic MMP2, and cytolytic granzyme B in the brain, which were both reduced after doxycycline.

Our results suggest that during ECM in addition to known anti-parasitic effects several systemic and local inflammatory processes are targeted by doxycycline, inhibiting BBB disruption and neuropathology. Thus we provide theoretical support for retaining doxycycline in the treatment of severe human malaria.