title: TNF-alpha, IL-1beta, IL-6, and cinc-1 levels in rat brain after meningitis induced by Streptococcus pneumoniae.
abstract: Bacterial meningitis caused by Streptococcus pneumoniae is associated with a significant mortality rate and persisting neurologic sequelae, including sensory-motor deficits, seizures, and impairment of learning and memory. The presence of proliferating bacteria within the subarachnoid and ventricular space compartments triggers an intense inflammatory host response at killing the invading microorganism. Proinflammatory mediators released in the process, including tumor necrosis factor alpha (TNF-alpha), interleukin (IL)-1beta, and IL-6, were shown to contribute to the development of brain injury in bacterial meningitis. Thus, the aim of this study was to verify the levels of the TNF-alpha, IL-1beta, IL-6, and CINC-1 in the rat brain after pneumococcal meningitis. The animals underwent a magna cistern tap receiving either 10 microL of sterile saline as a placebo or an equivalent volume of a S. pneumoniae suspension at the concentration of 5x10(9) cfu/mL. The placebo group was killed immediately after the induction and the meningitis group at 0, 6, 12, 24, 48, and 96h after induction. The brains were removed followed by the isolation of the hippocampus and prefrontal cortex for determining TNF-alpha, IL-1beta, IL-6, and CINC-1 levels. In the hippocampus we found increased levels of the TNF-alpha only at 6h (p<0.01; F=3.777); CINC-1 levels increased at 6 and 24h (p<0.001; p<0.05; F=15.05); and IL-6 and IL-1beta levels were not altered. In the prefrontal cortex, the TNF-alpha levels were found to be increased only at 6h (p<0.05; F=4.921); IL-6 (p<0.05; F=11.69) and IL-1beta (p<0.001; F=132.0) levels were found to be increased only at 24h after meningitis induction; and CINC-1 levels were found to be increased at 6, 12, and 24h (p<0.01; p<0.01; p<0.01; F=16.86) after meningitis induction. Our data suggest that cytokine/chemokine levels can be putative biomarkers of brain damage in the first hours of the pneumococcal meningitis.
authors.affiliation: Instituto Nacional de Ciência e Tecnologia Translacional em Medicina, Unidade Acadêmica de Ciências da Saúde, Universidade do Extremo Sul Catarinense, Criciúma, SC, Brazil. tba@unesc.net
authors.forename: Tatiana
authors.initials: T
authors.lastname: Barichello
authors.forename: Ivonete
authors.initials: I
authors.lastname: dos Santos
authors.forename: Geovana D
authors.initials: GD
authors.lastname: Savi
authors.forename: Lutiana R
authors.initials: LR
authors.lastname: Simões
authors.forename: Tiago
authors.initials: T
authors.lastname: Silvestre
authors.forename: Clarissa M
authors.initials: CM
authors.lastname: Comim
authors.forename: Daniela
authors.initials: D
authors.lastname: Sachs
authors.forename: Mauro M
authors.initials: MM
authors.lastname: Teixeira
authors.forename: Antonio L
authors.initials: AL
authors.lastname: Teixeira
authors.forename: João
authors.initials: J
authors.lastname: Quevedo
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001921:Brain / Q000378:metabolism* / Q000382:microbiology; D054360:Chemokine CXCL1 / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism*; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005786:Gene Expression Regulation / Q000502:physiology*; D053583:Interleukin-1beta / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism*; D008297:Male; D008586:Meningitis, Pneumococcal / Q000503:physiopathology*; D011008:Pneumococcal Infections / Q000503:physiopathology*; D051381:Rats; D017208:Rats, Wistar; D013296:Streptococcus pneumoniae / Q000502:physiology; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D054360:Chemokine CXCL1; C513297:Cxcl1 protein, rat; D016207:Cytokines; D053583:Interleukin-1beta; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha