Increase in IL-6 levels among major depressive disorder patients after a 6-week treatment with duloxetine 60 mg/day: a preliminary observation

Immune modifications, including changes in interleukin (IL)-6 levels, have often been observed in major depressive disorder (MDD) during treatment with selective serotonin reuptake inhibitors (SSRIs) or the serotonin norepinephrine reuptake inhibitor (SNRI) venlafaxine. Nevertheless, no equivalent observation for the SNRI duloxetine has been made to date

AIRE polymorphism, melanoma antigen-specific T cell immunity, and susceptibility to melanoma

AIRE is involved in susceptibility to melanoma perhaps regulating T cell immunity against melanoma antigens (MA). To address this issue, AIRE and MAGEB2 expressions were measured by real time PCR in medullary thymic epithelial cells (mTECs) from two strains of C57BL/6 mice bearing either T or C allelic variant of the rs1800522 AIRE SNP. Moreover, the extent of apoptosis induced by mTECs in MAGEB2-specific T cells and the susceptibility to in vivo melanoma B16F10 cell challenge were compared in the two mouse strains. The C allelic variant, protective in humans against melanoma, induced lower AIRE and MAGEB2 expression in C57BL/6 mouse mTECs than the T allele. Moreover, mTECs expressing the C allelic variant induced lower extent of apoptosis in MAGEB2-specific syngeneic T cells than mTECs bearing the T allelic variant (p < 0.05). Vaccination against MAGEB2 induced higher frequency of MAGEB2-specific CTL and exerted higher protective effect against melanoma development in mice bearing the CC AIRE genotype than in those bearing the TT one (p < 0.05). These findings show that allelic variants of one AIRE SNP may differentially shape the MA-specific T cell repertoire potentially influencing susceptibility to melanoma

Increase in IL-6 levels among major depressive disorder patients after a 6-week treatment with duloxetine 60 mg/day: a preliminary observation

Michele Fornaro1, Matteo Martino1, Florinda Battaglia2, Salvatore Colicchio3, Giulio Perugi41Department of Neuroscience, Section of Psychiatry, University of Genova, Genoa, Italy; 2Center of Excellence for Biomedical Research (CEBR), Genoa, Italy; 3Department of Neurosciences, Catholic University, Rome, Italy; 4Department of Psychiatry, Institute of Behavioral Sciences, University of Pisa, Pisa, ItalyBackground: Immune modifications, including changes in interleukin (IL)-6 levels, have often been observed in major depressive disorder (MDD) during treatment with selective serotonin reuptake inhibitors (SSRIs) or the serotonin norepinephrine reuptake inhibitor (SNRI) venlafaxine. Nevertheless, no equivalent observation for the SNRI duloxetine has been made to date.Method: Sixteen patients diagnosed with MDD and an actual major depressive episode according to DSM-IV criteria and 16 healthy controls entered a 6-week trial with duloxetine 60 mg/day. All subjects (n = 32) were assessed using the Hamilton Depression Rating Scale (HAM-D), the Young Mania Rating Scale (YMRS), and were monitored for IL-6 levels both at baseline and at week 6. Blood samples for IL-6 levels were evaluated by ELISA.Results: After 6 weeks of treatment, the mean total scores for HAM-D declined both in the depressed and control groups, while IL-6 modification showed an opposite trend both in depressed (12.38 &amp;plusmn; 19.80 to 19.73 &amp;plusmn; 18.94 pg/mL) and control subjects (12.25 &amp;plusmn; 21.12 to 17.63 &amp;plusmn; 20.44 pg/mL), as did YMRS (ns), although none of the subjects switched to (hypo)mania. Of note, IL-6 levels increased significantly only in the responders subgroup (n = 9; P = 0.012).Conclusion: The small sample size and weak design of this study limit the validity of our results, which should be regarded as preliminary only. Nonetheless, the trend of increasing IL-6 levels observed in responder patients treated with duloxetine should prompt further controlled, extended studies with larger samples, with the specific aim of better assessing a putative differential role of norepinephrinergic antidepressant stimulation of serotonergic reuptake inhibition in determining modifications in IL-6 levels. Ideally, more accurate replication studies may contribute to further understanding of the complex interaction of mood, antidepressant response, and the immune system.Keywords: interleukin-6 (IL-6), duloxetine, major depressive disorder (MDD)&amp;nbsp

Early and repeated IgG1Fc-pCons chimera vaccinations (GX101) improve the outcome in SLE-prone mice

A previous study showed that a tolerogenic gene vaccine based on a IgG1Fc-pCons chimera (here named GX101) protects NZB/NZW mice from SLE development. The present study was aimed at identifying the most effective schedule of immunization and the possible involvement of CD4(+)&nbsp;Foxp3(+)&nbsp;Treg in the mechanism of action, in view of its eventual translation to the human studies. NZB/NZW mice were vaccinated with B lymphocytes made transgenic by spontaneous transgenesis with a gene coding for a chimeric IgG1Fc-pCons construct. Different schedules of vaccination were set in relation to the timing and number of administrations. Survival, proteinuria levels, and CD4(+) Foxp3(+) Treg frequency were monitored during the full experiments. GX101-treated mice showed delayed disease onset and delayed mortality than controls. GX101 effects were implemented by early as well as repeated vaccine administrations. GX101 vaccination was associated with increased frequencies of CD4(+)&nbsp;CD25(+)&nbsp;Foxp3(+)&nbsp;Treg with respect to controls. This study demonstrates that early and repeated immunizations with GX101 vaccine provide a better outcome than late or single vaccine administration regarding onset/development in SLE-prone mice, acting as a possible disease-modifying approach. Vaccine effects are likely related to CD4(+)&nbsp;Foxp3(+)&nbsp;Treg cell expansion

Increased CD38 expression on T lymphocytes as a marker of HIV dissemination into the central nervous system

Cross-sectional analysis on 20 HIV-1 patients with neurological symptoms admitted to two infectious disease units. Cut-off of HIV-RNA (VL) was 20\u200acopies/ml for plasma and cerebral spinal fluid (CSF). Flow cytometry was used to analyze the phenotype of circulating and CSF T lymphocytes. CD38 mean fluorescence intensity (MFI) was higher on circulating CD4(+)T lymphocytes from patients with VL >20\u200acopies/ml in plasma (P =\u2009 0.001) or CSF (P =\u2009 0.001). The frequency of circulating CD8(+)CD38(+)T cells and CD38 MFI on these cells were higher in patients with VL >20\u200acopies/ml than in those with undetectable plasma VL (P =\u2009 0.030 and P =\u2009 0.023). The frequency of CSF CD4(+)CD38(+)T, as well as their CD38 and CD95 MFI, were increased in patients with detectable than non-detectable plasma VL (P =\u2009 0.01, P =\u2009 0.03, and P =\u2009 0.05). The % CD38(+)CD8(+)T in CSF correlated with time of virological suppression (\u3c1 =\u2009 -\u20090.462, P =\u2009 0.040) and the CNS penetration-effectiveness (CPE) score (\u3c1 =\u2009 -\u20090.467, P\u2009=\u20090.038). In conclusion, (a) the expression of CD38(+) on both CD4(+), CD8(+)T lymphocytes from peripheral blood and CSF discriminated between viremic and non-viremic patients and (b) T cell activation/apoptosis markers inversely correlated with CPE to remark the importance for therapy to restore immunological functions