CTRP-3 is permeable to the blood-brain barrier and is not regulated by glucose or lipids in vivo.

BACKGROUND: C1q/TNF-related protein-3 (CTRP-3) represents a novel anti-inflammatory and antidiabetic adipokine secreted by adipose tissue. The physiological and postprandial regulation of CTRP-3 remains obscure and it is not known whether CTRP-3 is permeable to the brain. The postprandial regulation of CTRP-3 during an oral glucose tolerance test (n = 100) and an oral lipid tolerance test (n = 100) in humans was investigated. Moreover, CTRP-3 concentrations were measured in paired serum and cerebrospinal fluid (CSF) samples of patients (n = 270) undergoing neurological evaluation. The expression of CTRP-3 mRNA was investigated in adipocytes upon stimulation with glucose, sex hormones and a broad panel of fatty acids. MATERIALS AND METHODS: Serum and CSF CTRP-3 concentrations were measured by ELISA. 3T3-L1 adipocytes were used for stimulation experiments. CTRP-3 mRNA expression was quantified by using real-time PCR analysis. RESULTS: CTRP-3 is present in human cerebrospinal fluid with a mean CSF/serum ratio of 110 ± 64 × 10-3 . CTRP-3 is not regulated postprandially by carbohydrates or lipids in the healthy state. Females have slightly higher levels of CTRP-3 when compared to males. A significant and positive correlation of CTRP-3 to LDL cholesterol serum levels is reproducible in several cohorts and deserves further mechanistic investigation. Whereas glucose concentrations do not influence CTRP-3 mRNA expression in 3T3-L1 adipocytes in vitro, fatty acids differentially modulate CTRP-3 expression. CONCLUSIONS: The novel adipokine CTRP-3 is detectable in human cerebrospinal fluid (proof of principle). Due to its blood-brain barrier permeability, CTRP-3 represents a novel putative candidate for a physiological regulator molecule affecting central nervous functions.

Utility of TWEAK to assess neuropsychiatric disease activity in systemic lupus erhytematosus.

OBJECTIVE: The purpose of this study was to assess the utility of tumor necrosis factor (TNF)-like weak inducer of apoptosis (TWEAK) in serum and cerebrospinal fluid (CSF) as a biomarker in neuropsychiatric systemic lupus erythematosus (NPSLE). METHODS: Thirty three NPSLE patients were evaluated at hospitalization and six months later. As controls, five SLE patients with septic meningitis, 51 hospitalized SLE patients without a history of neuropsychiatric (NP) manifestations and without infections, 16 SLE patients without NP manifestations (surgical-SLE), four patients with primary neuropsychiatric disorders, and 25 patients with non-autoimmune diseases were also studied. Serum and CSF samples were drawn at hospitalization, except non-NPSLE patients, in whom only serum was studied, and six months later in 19 NPSLE and 27 non-NPSLE patients. Serum and CSF TWEAK levels were measured by ELISA; values are expressed in pg/mL. RESULTS: The mean ± SD age of NPSLE patients was 31 ± 13.1 years, which was similar across study groups (p = 0.54). TWEAK levels in serum were not different across the study groups. In CSF, TWEAK levels were higher in NPSLE, surgical-SLE and primary neuropsychiatric groups than in non-autoimmune patients: median (IQR) 159.2 (94.1-374.9), 172.3 (125.3-421.9), 371.3 (143-543) vs. 122.1 (76.1-212.4), respectively; all p < 0.05. Six months later, when the neuropsychiatric manifestations were clinically in remission, serum or CSF TWEAK did not vary from baseline in NPSLE patients. CONCLUSIONS: TWEAK levels are slightly elevated in CSF in SLE patients compared with non-autoimmune controls, irrespective of the presence of NP manifestations. TWEAK levels in serum and CSF do not seem to be a useful biomarker of CNS involvement in SLE.

TWEAK is expressed at the cell surface of monocytes during multiple sclerosis.

The TNF superfamily ligand, TNF-like weak inducer of apoptosis (TWEAK), regulates cellular responses ranging from proliferation to cell death in a manner highly dependent on the cell type and the microenvironmental context. We have shown previously that treatment of experimental autoimmune encephalomyelitis mice after the priming phase with neutralizing anti-TWEAK antibodies results in a reduction in the severity of the disease and leukocyte infiltration. To further characterize TWEAK/fibroblast growth factor-inducible 14-kDa protein (Fn14) involvement during multiple sclerosis (MS), we evaluated in MS patients and controls: TWEAK and Fn14 expression on PBMC and soluble TWEAK concentration in serum and cerebrospinal fluid (CSF). Thirty-six consecutive patients were enrolled, including 11 patients with relapsing-remitting MS, 11 with a clinical isolated syndrome suggestive of MS (CISSMS), and 14 controls with non-MS diseases. Intracellular TWEAK could be observed in lymphocytes and/or monocytes in all groups of patients. None of the 36 patients displayed TWEAK expression at the cell surface of lymphocytes. In contrast, 12 out of the 36 patients were positive for membrane TWEAK expression on their monocytes. Among these patients, eight were from the CISSMS group. Fn14 was not detected in PBMC. The soluble form of TWEAK is detectable in serum and CSF of patients, and TWEAK concentrations were not statistically different between the disease groups. We demonstrated for the first time that TWEAK is expressed at the cell surface of monocytes during MS, especially in the CISSMS group. Our results support the proposal that TWEAK could be a target for antibody therapy in MS.

Valor pronóstico y discriminatorio de TNF alfa humano en niños con Meningitis / Predictive and discriminating value of TNF Alfa in children with meningitis

Se realizó un estudio exploratorio transversal descriptivo . La muestra se seleccionó entre los pacientes que ingresaron en la Unidad de Cuidados Intensivos del Hospital Pediátrico Juan Manuel Márquez de La Habana y los que asistieron a la Unidad de Emergencias del Hospital Pediátrico de Matanzas en el período comprendido entre los meses de marzo y agosto del año 2003. Con el objetivo de cuantificar los niveles de Tumor Necrosis Factor (TNF) en el líquido cefalorraquídeo y el suero, se utilizó un ensayo tipo ELISA. En el caso del tumor necrosis factor, no se encontraron diferencias entre su concentración en el líquido cefalorraquídeo y el suero en los pacientes incluidos en el estudio, ni entre los niveles de esta citosina en cada fluido biológico en relación con el tipo de meningitis. Sin embargo, el análisis de la presencia de niveles de TNF - ? superiores al límite de detección del método empleado (50 pg/mL) reveló que en todos los pacientes con meningitis bacteriana se detectó TNF- ? en el líquido cefalorraquídeo (6/6), mientras que sólo en el 50 por ciento de los pacientes con meningitis aséptica (6/12) se pudo demostrar la presencia de esta citosina pro-inflamatoria en el líquido cefalorraquídeo. No obstante, esta diferencia no alcanzó significación estadística(AU)

A descriptive, transversal, exploratory study was carried out in children with meningitis. The sample was chosen among the patients admitted in the Intensive Care Unit of the Pediatric Hospital Juan Manuel Marquez in Havana City and among those who attended the Emergency Unit of the Matanzas Pediatric Hospital in the period between March and August 2003. An ELISA test was used with the objective of quantifying TNF-? levels in cephalorachideal liquids and serum. In the case of TNF-?, there were not found concentration differences in cephalorachideal liquids and in serum in the patients included in this study, nor between the levels of this cytosine in every biological fluid in relation with the kind of meningitis. However, the analysis of the presence TNF-? levels higher than the detection limits of the used methods (50 pg/mL) showed that TNF-? in cephalorachideal liquids (6/6) was detected in all the patients suffering bacterial meningitis, while the presence of this pro-inflammatory cytosine in cephalorachideal liquids was found in only 50 por ciento of the patients with aseptic meningitis (6/12). Nevertheless, this difference did not reach statistic significance(AU)