Suppressor of cytokine signaling 2 (SOCS2) contributes to encephalitis in a model of Herpes infection in mice.

The most severe manifestation of Herpes Simplex Type 1 virus (HSV-1) infection is encephalitis characterized by arousal impairment and seizures that can evolve to coma and death. Previous studies reported the involvement of suppressor of cytokine signaling (SOCS) proteins, specifically SOCS1 and SOCS3, in HSV-1 infection, suggesting that other members of this family could be involved in the immune response against HSV-1. No previous study has reported the role of SOCS2 in HSV-1 infection. In the current study, C57BL/6 wild-type mice (WT) and mice deficient in SOCS2 gene (SOCS2-/-) were subjected to intracranial inoculation with 102 plaque forming units (PFU) of HSV-1. Survival curve, neuroinflammatory parameters and neuropathology were evaluated. Infected SOCS2-/- mice had increased survival in comparison with infected WT animals. This better outcome was associated with reduced leukocyte infiltration, concentration of cytokines, and structural changes in the brain. SOCS2 seems to play a detrimental role in HSV-1 encephalitis. Moreover, the control of neuroinflammatory response in HSV-1 infection was of paramount importance to clinical outcome.

Brain-blood barrier breakdown and pro-inflammatory mediators in neonate rats submitted meningitis by Streptococcus pneumoniae.

Neonatal meningitis is an illness characterized by inflammation of the meninges and occurring within the birth and the first 28 days of life. Invasive infection by Streptococcus pneumoniae, meningitis and sepsis, in neonate is associated with prolonged rupture of membranes; maternal colonization/illness, prematurity, high mortality and 50% of cases have some form of disability. For this purpose, we measured brain levels of TNF-α, IL-1ß, IL-6, IL-10, CINC-1, oxidative damage, enzymatic defense activity and the blood-brain barrier (BBB) integrity in neonatal Wistar rats submitted to pneumococcal meningitis. The cytokines increased prior to the BBB breakdown and this breakdown occurred in the hippocampus at 18 h and in the cortex at 12h after pneumococcal meningitis induction. The time-dependent association between the complex interactions among cytokines, chemokine may be responsible for the BBB breakdown and neonatal pneumococcal severity.

Serum levels of chemokines in Parkinson's disease.

OBJECTIVE: Neuroinflammatory processes seem to contribute to the degeneration of dopaminergic neurons in Parkinson's disease (PD). Chemokines play a role in the pathogenesis of inflammatory diseases, acting mainly as mediators of leukocyte recruitment to inflammatory sites. The aim of the present study was to compare the serum levels of chemokines between healthy subjects and PD patients and to correlate these levels with the severity of PD. METHODS: We used ELISA to measure the levels of CCL3, CCL11, CCL24, CXCL8 and CXCL10 chemokines in the serum of PD patients (n = 47) and age- and gender-matched controls (n = 23). Patients were also clinically evaluated with the Unified Parkinson's Disease Rating Scale, the Modified Hoehn and Yahr Staging Scale and the Modified Schwab and England Activities of Daily Living Scale. RESULTS: There was no significant difference in serum levels of chemokines between controls and PD patients. There was no correlation between the serum levels of chemokines and the clinical measures of disease severity. CONCLUSIONS: These findings suggest that serum levels of chemokines may not be considered as potential biomarkers of PD.

Anxiety-like behavior and proinflammatory cytokine levels in the brain of C57BL/6 mice infected with Plasmodium berghei (strain ANKA).

Cerebral malaria (CM) is a severe complication resulting from Plasmodium falciparum infection. The underlying mechanisms of CM pathogenesis remain incompletely understood. The imbalance between the release of proinflammatory and anti-inflammatory cytokines has been associated with central nervous system dysfunction found in human and experimental CM. The current study investigated anxiety-like behavior, histopathological changes and release of brain cytokines in C57BL/6 mice infected with Plasmodium berghei strain ANKA (PbA). Anxiety-like behavior was assessed in control and PbA-infected mice using the elevated plus maze test. Histopathological changes in brain tissue were assessed by haematoxylin and eosin staining. Brain concentration of the cytokines IL-1ß, IL-4, IL-10, TNF-α and IFN-γ was determined by ELISA. We found that PbA-infected mice on day 5 post-infection presented anxiety symptoms, histopathological alterations in the brainstem, cerebrum and hippocampus and increased cerebral levels of proinflammatory cytokines IL-1ß and TNF-α. These findings suggest an involvement of central nervous system inflammatory mediators in anxiety symptoms found in CM.