Evidence for an immune role on cognition in schizophrenia: a systematic review.

OBJECTIVE: Recent evidence has associated immune and inflammatory changes to cognitive performance in many diseases, including schizophrenia. Since this is a new research field where concepts are not yet solid and new questions and hypothesis are still arising, the present study aimed at summarizing the available clinical data associating schizophrenia, cognition and inflammation/immune function. METHODS: A SYSTEMATIC REVIEW OF THE LITERATURE WAS MADE BY SEARCHING THE FOLLOWING TERMS IN MEDLINE: "schizophrenia or psychosis or psychotic" AND "inflamm* or immun* or cytokine or IL-* or TNF-* or kynureni* or KYNA", AND "cognit* or attention or memory or executive function". RESULTS: Seventy five papers were identified using the selected terms, and seven papers were included in the review. Papers excluded focused mainly on basic research or other neuropsychiatric disorders. CONCLUSIONS: Recent findings link inflammatory markers to cognition in schizophrenia, suggesting that inflammation is associated with worst cognitive performance. Microglial activation, monoaminergic imbalance, brain abnormalities and the kynurenine pathway are possible mechanisms underlying cognitive impairment in schizophrenia. Clinical trials with addition of immunomodulatory drugs have shown promising results, opening new windows to tackle cognition in schizophrenia.

Absence of TNFR1 promotes a protective response in the early phase of hepatic encephalopathy induced by thioacetamide in mice.

Hepatic encephalopathy (HE) is a neuropsychiatric syndrome with a wide spectrum of cognitive deficits, motor impairment, and psychiatric disturbances resulting from liver damage. The cytokine TNF has been considered the main cytokine in the development and progression of HE, with a pivotal role in the initiation and amplification of the inflammatory cascade. The aim of the present study was to evaluate the involvement of TNF type 1 receptor (TNFR1) in locomotor deficits and in the levels of TNF, IFN-γ, IL-6, IL-10, IL-12p70, CCL2, CX3CL1 and BDNF from the frontal cortex and hippocampus of TNFR1 knockout mice (TNFR1-/-) mice with HE induced by thioacetamide. Wild-type (WT) animals with HE developed locomotor deficit. The absence of TNFR1 absence of TNFR1 in HE animals attenuated the locomotor activity impairment in parallel with a balanced neuroinflammatory environment 24 h after the administration of thioacetamide. Taken together, the data suggests that the absence of TNFR1 promoted a protective response in the early phase of hepatic encephalopathy induced by thioacetamide in mice.

NLRP3 and NLRP1 inflammasomes are up-regulated in patients with mesial temporal lobe epilepsy and may contribute to overexpression of caspase-1 and IL-ß in sclerotic hippocampi.

Inflammation plays a role in the pathophysiology of mesial temporal lobe epilepsy (MTLE). Inflammasome pathways, including the NLRP1 and NLRP3-induced ones, promote neuroinflammation and pyroptosis through interleukin (IL)-1ß and caspase-1 action. Evaluation of NLRP1 in sclerotic hippocampi is scarce and there are no data on NLRP3 in human TLE. The aim of this study was to evaluate the expression of these proteins alongside caspase-1 and IL-1ß in the hippocampi of patients with TLE compared to control samples. We also sought to investigate peripheral levels of caspase-1 and IL-1ß in an independent cohort. Sclerotic and control hippocampi were collected for both histological and immunohistochemical analyses of NLRP1, NLRP3, caspase-1 and IL-1ß; plasma was sampled for the measurement of caspase-1 and IL-1ß levels through enzyme-linked immunoassay (ELISA) and cytometric bead array (CBA). Sclerotic hippocampi displayed higher expression of the measured proteins than control. Both glia and neurons showed activation of these pathways. Additionally, increased expression of NLRP1 and NLRP3 was associated with elevated plasma levels of IL-1ß and in TLE, and increased levels of peripheral caspase-1 were associated with bilateral hippocampal sclerosis (HS). In conclusion, NLRP1 and NLRP3 are up-regulated in sclerotic hippocampi, what may be responsible, at least in part, for the increased hippocampal expression of caspase-1 and IL-1ß. Our data suggest a role for inflammasome activation in central and peripheral inflammation in TLE.

Is chronic periodontitis premature in systemic lupus erythematosus patients?

The aim of this study was to compare the frequency and severity of chronic periodontitis (CP) in systemic lupus erythematosus (SLE) patients with individuals without rheumatic diseases. Seventy-five patients with SLE were compared to 75 individuals without rheumatic diseases (control group) matched for age, educational level, and income. The activity of SLE was assessed with the Systemic Lupus Erythematosus Disease Activity Index 2000. Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index for Systemic Lupus Erythematosus evaluated SLE-related damage. Dental evaluation included measuring plaque index and parameters of periodontal disease (probing depth, clinical attachment level, and bleeding on probing). Fifty-one (68 %) SLE patients and 42 (56 %) control individuals had CP (p = 0.13). Periodontal status was similar in both groups. Considering only individuals with CP, SLE patients were younger than controls (40.7 ± 9.8 versus 46.14 ± 12.5 years of age, p = 0.02). CP was not associated with activity or therapeutics in SLE patients. Severity of periodontal parameters was similar in SLE patients and control subjects; however, CP occurred earlier in SLE patients.

Role of the suppressor of cytokine signaling 2 (SOCS2) during meningoencephalitis caused by Bovine herpesvirus 5 (BoHV-5).

The role of suppressors of cytokine signaling (SOCS) in meningoencephalitis caused by Bovine herpesvirus 5 (BoHV-5) was evaluated by intracranial infection in C57BL/6 wild-type mice (WT) and SOCS2 deficient mice (SOCS2(-/-)). Both infected groups presented weight loss, ruffled fur and hunched posture. Additionally, infected SOCS2(-/-) mice showed swollen chamfer and progressive depression. Infected WT animals developed mild meningitis, characterized by infiltration of mononuclear cells. Moreover, viral DNA was detected in liver and lung from infected WT group. This group also showed elevated brain levels of IFN-γ, IL-10, CXCL1 and CCL5, when compared with non-infected WT animals. Brain inflammation was exacerbated in infected SOCS2(-/-) mice with widespread distribution of the virus and increased brain levels of TNF-α, IFN-γ, IL-10, IL-12, CXCL1 and CCL5, when compared with WT infected mice. Moreover, infected SOCS2 deficient mice exhibited reduced brain mRNA expression of IFNα and IFNß and increased expression of mRNA of SOCS1, compared with infected WT mice. Taken together, our study provides an insight into the role of SOCS2 in modulating the immune response to BoHV-5 infection.

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.