title: Interleukin-1β Receptor Antagonism Prevents Cognitive Impairment Following Experimental Bacterial Meningitis.
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 brain-derived 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.
authors.affiliation: Laboratório de Microbiologia Experimental, PPGCS, UNASAU, Universidade do Extremo Sul Catarinense, 88806-000 Criciúma, SC, Brazil. tba@unesc.net.
authors.forename: Tatiana
authors.initials: T
authors.lastname: Barichello
authors.forename: Jaqueline S
authors.initials: JS
authors.lastname: Generoso
authors.forename: Lutiana R
authors.initials: LR
authors.lastname: Simões
authors.forename: Vladislav G
authors.initials: VG
authors.lastname: Sharin
authors.forename: Renan A
authors.initials: RA
authors.lastname: Ceretta
authors.forename: Diogo
authors.initials: D
authors.lastname: Dominguini
authors.forename: Clarissa M
authors.initials: CM
authors.lastname: Comim
authors.forename: Márcia C
authors.initials: MC
authors.lastname: Vilela
authors.forename: Antonio Lucio
authors.initials: AL
authors.lastname: Teixeira
authors.forename: João
authors.initials: J
authors.lastname: Quevedo
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D003072:Cognition Disorders / Q000209:etiology* / Q000517:prevention & control*; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D005106:Exploratory Behavior / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects; D007266:Inhibition, Psychological; D053590:Interleukin 1 Receptor Antagonist Protein / Q000627:therapeutic use*; D008297:Male; D016920:Meningitis, Bacterial / Q000150:complications*; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar; D021641:Recognition, Psychology / Q000187:drug effects; D013296:Streptococcus pneumoniae / Q000472:pathogenicity
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D016207:Cytokines; D053590:Interleukin 1 Receptor Antagonist Protein; D018696:Neuroprotective Agents