scholarly journals Improvements in Immune Function and Activation with 48-Week Darunavir/Ritonavir-Based Therapy: GRACE Substudy

ISRN AIDS ◽  
2013 ◽  
Vol 2013 ◽  
pp. 1-10 ◽  
Author(s):  
Christos Tsoukas ◽  
Louise Gilbert ◽  
Trevor Lewis ◽  
George Hatzakis ◽  
Ron Falcon ◽  
...  
Keyword(s):  
Interleukin 2 ◽  
Cd4 Cells ◽  
Cell Recovery ◽  
Necrosis Factor Alpha ◽  
Cd4 Cell Count ◽  
Functional Immunity ◽  
Factor Alpha ◽  
Cd4 Cell ◽  
Hiv 1 ◽  
Necrosis Factor

Objective. During the course of HIV infection, progressive immune deficiency occurs. The aim of this prospective substudy was to evaluate the recovery of functional immunity in a subset of patients from the GRACE (Gender, Race, And Clinical Experience) study treated with a DRV/r-based regimen. Methods. The recovery of functional immunity with a darunavir/ritonavir-based regimen was assessed in a subset of treatment-experienced, HIV-1 infected patients from the GRACE study. Results. 19/32 patients (59%) enrolled in the substudy were virologically suppressed (<50 copies/mL). In these patients, median (range) CD4+ cell count increased from 222 (2, 398) cells/mm3 at baseline to 398 (119, 812) cells/mm3 at Week 48. CD8+% decreased significantly from baseline to Week 48 (P=.03). Proliferation of CD4+ lymphocytes in response to CD3+/CD28+, phytohemagglutinin, and pokeweed was significantly increased (P<.01) by Week 12. Proliferation in response to Candida and tetanus was significantly increased by Week 48 (P<.01 and P=.014, resp.). Staphylococcal enterotoxin B-stimulated tumor necrosis factor-alpha and interleukin-2 in CD4+ cells was significantly increased by Week 12 (P=.046) and Week 48 (P<.01), respectively. Conclusions. Darunavir/ritonavir-based therapy demonstrated improvements in CD4+ cell recovery and association with progressive functional immune recovery over 48 weeks. This trial is registered with NCT00381303.

scholarly journals Different cytokine patterns associate with melancholia severity among inpatients with major depressive disorder

2020 ◽  
Vol 10 ◽  
pp. 204512532093792 ◽  
Author(s):  
Lucas Primo de Carvalho Alves ◽  
Neusa Sica da Rocha
Keyword(s):  
Depressed Mood ◽  
Rating Scale ◽  
Interleukin 2 ◽  
Psychomotor Retardation ◽  
Necrosis Factor Alpha ◽  
Depressed Patients ◽  
Tnf Α ◽  
Inflammatory Pattern ◽  
Factor Alpha ◽  
Necrosis Factor

Background Six melancholic features (MFs) of the Hamilton Depression Rating Scale (HAM-D6) represent the construct of melancholia along a continuum of severity (from least to most severe: depressed mood, work and activities, somatic symptoms, psychic anxiety, guilty feelings, psychomotor retardation). We aimed to evaluate the association between these MFs and inflammatory cytokines (IC) in the blood. Methods Each IC [interferon gamma (IFN-γ), tumor necrosis factor alpha (TNF-α), interleukin 2 (IL-2), IL-4, IL-6, IL-10, and IL-17] was associated with the HAM-D6 MFs of 139 severely depressed inpatients, using multiple linear regressions adjusted for covariates. Levels were compared with those of 100 healthy controls. Results Depressed mood was associated with higher levels of IL-4 ( β = 0.167; p = 0.041). Psychic anxiety: lower IL-17 levels ( β = –0.173; p = 0.039). Guilt feelings: lower IL-2 levels ( β = −0.168; p = 0.041) Psychomotor retardation: higher IL-6 levels ( β = 0.195; p = 0.017). Depressed patients’ TNF-α, INF-γ, and IL-4 levels were not significantly different from controls. Depressed patients’ IL-2, IL-6, IL-10, and IL-17 levels were higher than those of controls ( p <0.001). Conclusion Less severe MFs (depressed mood, psychic anxiety, and guilt feelings) were associated with an anti-inflammatory pattern (higher IL-4, lower IL-17 and lower IL-2, respectively). The presence of the most severe MF, psychomotor retardation, was associated with a higher pro-inflammatory response (higher IL-6).

scholarly journals Cytokines regulate HIV-1 replication and lymphocyte apoptosis in vitro

2013 ◽  
Vol 94 (6) ◽  
pp. 906-910 ◽  
Author(s):  
S V Boichuk ◽  
P D Dunaev ◽  
I G Mustafin
Keyword(s):  
Flow Cytometry ◽  
Tumor Necrosis Factor ◽  
Tumor Necrosis Factor Alpha ◽  
Tumor Necrosis ◽  
Lymphocyte Apoptosis ◽  
Necrosis Factor Alpha ◽  
Factor Alpha ◽  
Hiv 1 ◽  
Necrosis Factor

Aim. To study the ability of cytokines - interleukin-2, interleukin-7 and tumor necrosis factor alpha to induce human immunodeficiency virus type 1 (HIV-1) replication and lymphocyte apoptosis in vitro. Methods. Peripheral blood mononuclears were separated by centrifugation on a ficoll paque solution specific density gradient. Lymphocytes were cultivated in RPMI 1640 medium with addition of L-glutamine, embryonal bovine serum, antibiotics and cytokines (interleukines-2, -4, -7, tumor necrosis factor alpha). To infect the lymphocytes, a laboratory strain of HIV-1 NL4-3 (NIH ResReag. Prog., USA) was used. HIV-1 replication was assessed by р24gag viral protein level in culture supernatants (ELISA) and its cytozolic level in lymphocytes (flow cytometry). Lymphocyte apoptosis was assessed by flow cytometry using the following parameters: (1) decrease of transmembrane mitochondrial potential; (2) increase in phosphatidyl serine molecules expression. Lymphocyte activation was assessed by CD25 and HLA-DR molecules expression (flow cytometry). Results. Cytokines induce the HIV-1 replication in lymphocytes in vitro. HIV-1 replication was noted only if inactivated lymphocytes were present in the culture. At the same time, lymphocytes not expressing the classical activation markers (CD25 and HLA-DR) were present among the lymphocytes producing HIV-1 indicating the possible alternative mechanism of HIV-1 replication, not dependent on cell activation. This fact might also be an evidence of viral replication processes in the pool of latently-infected lymphocytes, not expressing the classic activation markers. The abovementioned cytokines promote apoptotic death of uninfected lymphocytes in vitro, backing up the infected cells viability and thus promoting HIV-1 replication. Conclusion. Cytokines (interleukines-2, -4, -7, tumor necrosis factor alpha) which are known as factors supporting the immune system homeostasis and immune response formation, might also play a negative role in HIV-1 pathogenesis - induce HIV-1 replication in lymphocytes and, probably, lead to reactivation of the pool of latently-infected lymphocytes, deepening the lymphopenia and leading to disease progression.

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