Title:Interleukin-1β Receptor Antagonism Prevents Cognitive Impairment Following Experimental Bacterial Meningitis
Volume: 12
Issue: 3
Author(s): Tatiana Barichello, Jaqueline S. Generoso, Lutiana R. Simoes, Vladislav G. Sharin, Renan A. Ceretta, Diogo Dominguini, Clarissa M. Comim, Marcia C. Vilela, Antonio Lucio Teixeira and Joao Quevedo
Affiliation:
Keywords:
Bacterial meningitis, cytokines, BDNF, hippocampus, behaviour.
Abstract: Pneumococcal meningitis is characterized by high rates of mortality and long-term cognitive impairment. In
this study, we evaluated the effects of interleukin (IL)-1β receptor antagonist (IL-1Ra) on memory, cytokine, and brainderived
neurotrophic factor (BDNF) levels in hippocampus after experimental pneumococcal meningitis. In a first experiment
the animals were divided into four groups: control/saline, control treated with IL-1Ra, meningitis/saline, and
meningitis treated with IL-1Ra. In the meningitis/saline group IL-1β and cytokine-induced neutrophil chemoattractant-1
(CINC-1) levels increased at 24 h post-infection; adjuvant treatment with IL-1Ra reversed the increased levels in the hippocampus.
The levels of tumour necrosis factor-alpha (TNF-α), IL-4, IL-6, IL-10, and BDNF did not change in all groups
at 24 h post-infection. In a second experiment, the animals were subjected to behavioural tasks (open field, step-down inhibitory
avoidance task, and object recognition task), cytokine, and BDNF levels analysis 10 days after experimental meningitis
induction. In the open-field task, the meningitis/saline group did not exhibit difference between the training and test
sessions, in the motor and exploratory activity indicating memory injury. The meningitis/IL-1Ra group presented difference
between training and test session indicating habituation memory. The meningitis/saline group showed impairment in
long-term memory for novel object recognition and in aversive memory. The adjuvant treatment with IL-1Ra prevented
memory impairment. After behavioural tasks the hippocampus was evaluated. The levels of IL-4, IL-6, IL-10, and BDNF
were maintained elevated 10 days post-infection. CINC-1 levels were elevated only in meningitis/saline group and IL-1β
decreased in meningitis/IL-Ra group. The levels of TNF-α did not change at 10 days post-infection. These findings illustrate
the anti-inflammatory activity of IL-1Ra inhibitor in the first hours after meningitis induction. Adjuvant treatment
with IL-1β receptor antagonist could be a new avenue as therapeutic target during bacterial meningitis.