Limits...
Divergent cerebrospinal fluid cytokine network induced by non-viral and different viral infections on the central nervous system.

Bastos MS, Coelho-Dos-Reis JG, Zauli DA, Naveca FG, Monte RL, Pimentel JP, Macário VM, da Silva NL, Peruhype-Magalhães V, Pascoal-Xavier MA, Guimaraes A, Carvalho AT, Malheiro A, Martins-Filho OA, Mourão MP - BMC Infect. Dis. (2015)

Bottom Line: 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).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).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.

View Article: PubMed Central - PubMed

Affiliation: Tropical Medicine Foundation Dr. Heitor Vieira Dourado, Manaus, AM, Brazil. michelebastos01@gmail.com.

ABSTRACT

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).

Conclusion: 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.

No MeSH data available.


Related in: MedlinePlus

Association of the cytokine profile of cerebrospinal fluid with cellularity in aseptic meningitis. The levels of TNF-α and IL-17 as well as cellularity were measured in the CSF as described in material and methods. Graphs of cellularity (x axis) versus cytokine (y axis) were plotted and each dot represents one patient from (top panels) virus not detected (undiagnosed) and (bottom panels) virus-positive meningoencephalitis groups. Dotted lines represent the global median of cellularity (vertical) and cytokine (horizontal) and the percentages express the frequency of patients in each quadrant
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

License 1 - License 2
getmorefigures.php?uid=PMC4541733&req=5

Fig4: Association of the cytokine profile of cerebrospinal fluid with cellularity in aseptic meningitis. The levels of TNF-α and IL-17 as well as cellularity were measured in the CSF as described in material and methods. Graphs of cellularity (x axis) versus cytokine (y axis) were plotted and each dot represents one patient from (top panels) virus not detected (undiagnosed) and (bottom panels) virus-positive meningoencephalitis groups. Dotted lines represent the global median of cellularity (vertical) and cytokine (horizontal) and the percentages express the frequency of patients in each quadrant

Mentions: Previously, the results demonstrated that TNF-α and IL17 were secreted in different magnitude in groups with high and low cellularity. Therefore, further analyses of these two cytokines were performed. First, the level of the cytokines and cellularity were correlated by plotting a “cellularity-versus-cytokine” dual-axis graph. The thresholds in the graph represent the global median values (horizontal = cellularity; Transversal = cytokine), which formed a 4-quarter dot-plot. Figure 4 displays the results for TNF-α and IL17 plots. The frequency of patients with viral meningoencephalitis (TNF-α and IL-17 = 55 %) was higher in the high cellularity quarters (top and bottom right) of the 4-quarter graph when compared to frequency of patients with undiagnosed meningoencephalitis in those quarters (TNF-α and IL-17 = 37–38 %). In addition, undiagnosed meningoencephalitis patients had higher values of the upper-left corner of the graph (high cytokine levels with low cellularity) for both TNF-α (39 %) and IL-17 (31 %) when compared to patients with virus-positive meningoencephalitis (TNF-α = 13 % and IL-17 = 5 %). Patients from the Enterovirus group are observed in the upper right corner of both graphs confirming that this group presents high cytokine production accompanied by greater cellularity.Fig. 4


Divergent cerebrospinal fluid cytokine network induced by non-viral and different viral infections on the central nervous system.

Bastos MS, Coelho-Dos-Reis JG, Zauli DA, Naveca FG, Monte RL, Pimentel JP, Macário VM, da Silva NL, Peruhype-Magalhães V, Pascoal-Xavier MA, Guimaraes A, Carvalho AT, Malheiro A, Martins-Filho OA, Mourão MP - BMC Infect. Dis. (2015)

Association of the cytokine profile of cerebrospinal fluid with cellularity in aseptic meningitis. The levels of TNF-α and IL-17 as well as cellularity were measured in the CSF as described in material and methods. Graphs of cellularity (x axis) versus cytokine (y axis) were plotted and each dot represents one patient from (top panels) virus not detected (undiagnosed) and (bottom panels) virus-positive meningoencephalitis groups. Dotted lines represent the global median of cellularity (vertical) and cytokine (horizontal) and the percentages express the frequency of patients in each quadrant
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4541733&req=5

Fig4: Association of the cytokine profile of cerebrospinal fluid with cellularity in aseptic meningitis. The levels of TNF-α and IL-17 as well as cellularity were measured in the CSF as described in material and methods. Graphs of cellularity (x axis) versus cytokine (y axis) were plotted and each dot represents one patient from (top panels) virus not detected (undiagnosed) and (bottom panels) virus-positive meningoencephalitis groups. Dotted lines represent the global median of cellularity (vertical) and cytokine (horizontal) and the percentages express the frequency of patients in each quadrant
Mentions: Previously, the results demonstrated that TNF-α and IL17 were secreted in different magnitude in groups with high and low cellularity. Therefore, further analyses of these two cytokines were performed. First, the level of the cytokines and cellularity were correlated by plotting a “cellularity-versus-cytokine” dual-axis graph. The thresholds in the graph represent the global median values (horizontal = cellularity; Transversal = cytokine), which formed a 4-quarter dot-plot. Figure 4 displays the results for TNF-α and IL17 plots. The frequency of patients with viral meningoencephalitis (TNF-α and IL-17 = 55 %) was higher in the high cellularity quarters (top and bottom right) of the 4-quarter graph when compared to frequency of patients with undiagnosed meningoencephalitis in those quarters (TNF-α and IL-17 = 37–38 %). In addition, undiagnosed meningoencephalitis patients had higher values of the upper-left corner of the graph (high cytokine levels with low cellularity) for both TNF-α (39 %) and IL-17 (31 %) when compared to patients with virus-positive meningoencephalitis (TNF-α = 13 % and IL-17 = 5 %). Patients from the Enterovirus group are observed in the upper right corner of both graphs confirming that this group presents high cytokine production accompanied by greater cellularity.Fig. 4

Bottom Line: 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).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).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.

View Article: PubMed Central - PubMed

Affiliation: Tropical Medicine Foundation Dr. Heitor Vieira Dourado, Manaus, AM, Brazil. michelebastos01@gmail.com.

ABSTRACT

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).

Conclusion: 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.

No MeSH data available.


Related in: MedlinePlus