Divergent cerebrospinal fluid cytokine network induced by non-viral and different viral infections on the central nervous system.
BACKGROUND
Meningoencephalitis is one of the most common disorders of the central nervous system (CNS) worldwide. Viral meningoencephalitis differs from bacterial meningitis in several aspects. In some developing countries, bacterial meningitis has appropriate clinical management and chemotherapy is available. Virus-associated and virus not detected meningoencephalitis are treatable, however, they may cause death in a few cases. The knowledge of how mediators of inflammation can induce disease would contribute for the design of affordable therapeutic strategies, as well as to the diagnosis of virus not detected and viral meningoencephalitis. Cytokine-induced inflammation to CNS requires several factors that are not fully understood yet.


METHODS
Considering this, several cytokines were measured in the cerebrospinal fluid (CSF) of patients with undiagnosed and viral meningoencephalitis, and these were correlated with cellularity in the CSF.


RESULTS
The results demonstrate that an altered biochemical profile alongside increased cellularity in the cerebrospinal fluid is a feature of patients with meningoencephalitis that are not associated with the detection of virus in the CNS (P < 0.05). Moreover, HIV-positive patients (n = 10) that evolve with meningoencephalitis display a distinct biochemical/cytological profile (P < 0.05) in the cerebrospinal fluid. Meningoencephalitis brings about a prominent intrathecal cytokine storm regardless of the detection of virus as presumable etiological agent. In the case of Enterovirus infection (n = 13), meningoencephalitis elicits robust intrathecal pro-inflammatory cytokine pattern and elevated cellularity when compared to herpesvirus (n = 15) and Arbovirus (n = 5) viral infections (P < 0.05).


CONCLUSIONS
Differences in the cytokine profile of the CSF may be unique if distinct, viral or presumably non-viral pathways initially trigger the inflammatory response in the CNS.
Tropical Medicine Foundation Dr. Heitor Vieira Dourado, Manaus, AM, Brazil. michelebastos01@gmail.com.
Michele Souza
MS
Bastos
Laboratory of Biomarkers for Diagnosis and Monitoring, René Rachou Research Center, FIOCRUZ, Av. Augusto de Lima 1715, Barro Preto, Belo Horizonte, Minas Gerais, CEP 30190-002, Brazil. jordana.reis@cpqrr.fiocruz.br.
Jordana Grazziela
JG
Coelho-Dos-Reis
Laboratory of Biomarkers for Diagnosis and Monitoring, René Rachou Research Center, FIOCRUZ, Av. Augusto de Lima 1715, Barro Preto, Belo Horizonte, Minas Gerais, CEP 30190-002, Brazil. daniellezauli@yahoo.com.br.|Instituto Hermes Pardini, Belo Horizonte, MG, Brazil. daniellezauli@yahoo.com.br.
Danielle Alves Gomes
DA
Zauli
Institute Leônidas and Maria Deane - Fiocruz Amazônia, Manaus, AM, Brazil. fnaveca@amazonia.fiocruz.br.
Felipe Gomes
FG
Naveca
Tropical Medicine Foundation Dr. Heitor Vieira Dourado, Manaus, AM, Brazil. rossi@fmt.am.gov.br.
Rossicleia Lins
RL
Monte
Hematology and Hemotherapic Foundation of Amazonas, Manaus, AM, Brazil. jpimentel@gmail.com.
João Paulo
JP
Pimentel
Tropical Medicine Foundation Dr. Heitor Vieira Dourado, Manaus, AM, Brazil. muni_kramer@hotmail.com.
Valéria Munique Kramer
VM
Macário
Tropical Medicine Foundation Dr. Heitor Vieira Dourado, Manaus, AM, Brazil. naty_lessa@hotmail.com.
Natália Lessa
NL
da Silva
Laboratory of Biomarkers for Diagnosis and Monitoring, René Rachou Research Center, FIOCRUZ, Av. Augusto de Lima 1715, Barro Preto, Belo Horizonte, Minas Gerais, CEP 30190-002, Brazil. vanessa@cpqrr.fiocruz.br.
Vanessa
V
Peruhype-Magalhães
Department of Anatomic Pathology, Medicine School, Federal University of Minas Gerais, Belo Horizonte, MG, Brazil. mapx13@gmail.com.
Marcelo Antônio
MA
Pascoal-Xavier
Hematology and Hemotherapic Foundation of Amazonas, Manaus, AM, Brazil. allyson.gui.costa@gmail.com.
Allyson
A
Guimaraes
Laboratory of Biomarkers for Diagnosis and Monitoring, René Rachou Research Center, FIOCRUZ, Av. Augusto de Lima 1715, Barro Preto, Belo Horizonte, Minas Gerais, CEP 30190-002, Brazil. atcteixeira@gmail.com.
Andréa Teixeira
AT
Carvalho
Hematology and Hemotherapic Foundation of Amazonas, Manaus, AM, Brazil. malheiroadriana@yahoo.com.br.
Adriana
A
Malheiro
Laboratory of Biomarkers for Diagnosis and Monitoring, René Rachou Research Center, FIOCRUZ, Av. Augusto de Lima 1715, Barro Preto, Belo Horizonte, Minas Gerais, CEP 30190-002, Brazil. oamfilho@cpqrr.fiocruz.br.
Olindo Assis
OA
Martins-Filho
Tropical Medicine Foundation Dr. Heitor Vieira Dourado, Manaus, AM, Brazil. mariapaula.mourao@gmail.com.|Amazonas State University, Manaus, AM, Brazil. mariapaula.mourao@gmail.com.
Maria Paula Gomes
MP
Mourão
D001102:Arbovirus Infections / Q000134:cerebrospinal fluid* / Q000175:diagnosis / Q000276:immunology; D020805:Central Nervous System Viral Diseases / Q000134:cerebrospinal fluid / Q000175:diagnosis / Q000276:immunology; D060085:Coinfection / Q000134:cerebrospinal fluid / Q000276:immunology; D003430:Cross-Sectional Studies; D016207:Cytokines / Q000134:cerebrospinal fluid* / Q000276:immunology; D004279:DNA, Viral / Q000134:cerebrospinal fluid; D004769:Enterovirus Infections / Q000134:cerebrospinal fluid* / Q000175:diagnosis / Q000276:immunology; D015658:HIV Infections / Q000134:cerebrospinal fluid* / Q000175:diagnosis / Q000276:immunology; D006566:Herpesviridae Infections / Q000134:cerebrospinal fluid* / Q000175:diagnosis / Q000276:immunology; D006801:Humans; D007249:Inflammation; D007371:Interferon-gamma / Q000134:cerebrospinal fluid / Q000276:immunology; D016753:Interleukin-10 / Q000134:cerebrospinal fluid / Q000276:immunology; D018664:Interleukin-12 / Q000134:cerebrospinal fluid / Q000276:immunology; D020381:Interleukin-17 / Q000134:cerebrospinal fluid / Q000276:immunology; D015850:Interleukin-6 / Q000134:cerebrospinal fluid / Q000276:immunology; D016180:Lentivirus Infections / Q000134:cerebrospinal fluid* / Q000276:immunology; D008590:Meningoencephalitis / Q000134:cerebrospinal fluid* / Q000175:diagnosis / Q000276:immunology; D012367:RNA, Viral / Q000134:cerebrospinal fluid; D014409:Tumor Necrosis Factor-alpha / Q000134:cerebrospinal fluid / Q000276:immunology
D016207:Cytokines; D004279:DNA, Viral; C508609:IL10 protein, human; C508717:IL17A protein, human; C508600:IL6 protein, human; D020381:Interleukin-17; D015850:Interleukin-6; D012367:RNA, Viral; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D018664:Interleukin-12; D007371:Interferon-gamma