Einfluss des antimikrobiellen Peptids Ac2-26 auf die Entzündungsreaktion in Folge einer bakteriellen Meningitis

Meningitis is still a serious infectious disease of the meninges. Although the brain is initially protected by the blood-brain barrier and the innate immune system, bacteria, viruses and other microorganisms manage to trigger meningitis, with the consequence of numerous neuronal late effects. The migrating pathogens are recognized by the immune cells by means of pattern recognition receptors, including the G-protein-coupled formyl peptide receptors (FPR). The FPR have a broad spectrum of possible ligands, which includes both pro-inflammatory and anti-inflammatory ligands. The two main representatives are FPR1 and FPR2.The aim of this study was to investigate the influence of the N-terminal fragment of the endogenous FPR agonist Annexin A1, Ac2-26, on the inflammatory response in a mouse model of pneumococcal meningitis. Wildtype, FPR1 and FPR2 knockout (KO) mice were intrathecally infected with Streptococcus pneumoniae D39 (type 2). The groups treated with Ac2-26 received intraperitoneal injections of 1 mg Ac2-26 per kg body weight 2, 8 and 24 hours after infection. The extent of inflammation in different regions of the mouse brain was analyzed by means of immunohistochemistry and real-time PCR (RT-PCR) 30 hours after infection. The results showed a positive modulation of the immune response by Ac2-26, which decreased glial cell activity and secretion of pro-inflammatory cytokines and reduced infiltration by neutrophil granulocytes. However, the anti-inflammatory cytokine release was not influenced by the ligand. Thus, the results show how important a coordinated immune response is to maintain the delicate balance between useful and harmful immune response in the brain