Humic substance-based antivirals: antiretroviral activity, mechanisms of action, and impact on mucosal immunityстатья
Статья опубликована в высокорейтинговом журнале
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Дата последнего поиска статьи во внешних источниках: 10 апреля 2018 г.
Аннотация:Introduction: Secondary immunodeficiency is the loss of immune
function as a result of exposure to disease agents, immunosuppression,
or aging. All secondary immunodeficiencies have been outdone
by AIDS that is caused by HIV. HIV directly infects a small number
of Th cells, and also impairs other immune system responses indirectly.
Despite the wide application of HAART, the number of HIVpositive
patients continues to grow steadily. This shows an urgent
need for a directed search for new antiviral drugs against HIV.
164 | ABSTRACTS
Objectives: The purpose of this study was to investigate the
antiretroviral activity of humic substances (HS), its mechanisms of
action, and impact on mucosal immunity. The evaluation of antiretroviral
efficacy of HS was performed using HIV-1 BRU and different
target cells (MT-4, CEM-SS). The level of virus replication was
detected by p24 HIV-1 antigen ELISA. Mechanisms of action were
evaluated in a Time of addition assay. Mucosal immunostimulatory
activity of HS evaluated in several in vitro cell models (PBMC,
macrophages and dendritic cells). Cytotoxicity was determined using
the MTT assay.
Results: The results showed that the HS fractions exhibited a distinct
antiviral activity within the concentration range from 0.78 ug/
mL to 100 ug/mL with respect to HIV-1. All fractions of HS from
peloids within the studied range of concentrations did not display
pronounced cytotoxicity. Time of addition assay show that HS have
antiviral activity at the stage of HIV fusion, and at the stage of
reverse transcription of DNA to RNA, and at the stage of integration
of viral DNA into the genome of the host cell. HS increased lymphocyte
proliferation of phytohaemagglutinin A (PHA) and pokeweed
mitogen (PWM) stimulated mononuclear lymphocytes (MNL) in vitro
from concentrations of 10 to 100 ug/mL. HS inhibited the release of
TNF-alpha, IL-1 beta, IL-6 and IL-10 by PHA stimulated MNL at 50
ug/mL.
Conclusions: The low cytotoxicity and high antiretroviral activity
of HS indicate that these substances hold significant promise as safe
and efficacious antiviral drugs for the treatment of secondary
immunodeficiency, such as HIV infection. The ability of HS to interfere
with multiple stages of the HIV replication cycle of is viewed as
an added benefit suggesting potential for further development as
antiviral drugs.
0487 | Functional characterization of T helper
cells in a cohort of common variable
immunodeficiency patients
Milota T; Kayserova J; Zachova R; Rataj M; Sediva A
2nd Faculty of Medicine Charles University and University Hospital in
Motol, Prague, Czech Republic
Introduction: Common Variable Immunodeficiency (CVID) is a
heterogenous group of disorders characterized by impaired
immunoglobulin production and dysregulation of immune system.
Dysregulation may manifest as lymphoproliferative, granulomatous
or autoimmune diseases. Autoimmunity occurs in 25-30% of CVID
patients according to available literature sources. The underlying
mechanisms have not been entirely revealed yet. Alterations in
innate as well as adaptive immunity have been described, however,
only few studies regarded T cell compartment were carried out. Particularly
abnormalities in T cell development were previously
reported such as reduction of recent thymic emigrants or reduction
of CD4+ T cells (primarily naive CD4+ T cells), specifically in CVID
patients with autoimmune complications. Moreover, there is also lack
of information about T-cells (Th cells respectively) functions. Therefore,
we initiated our study to characterize predominant immune
response (Th1, Th2 or Th17) and corresponding cytokine production
(IFN-gamma, IL-5, IL-17), expression of transcriptional factors (T-Bet,
GATA-3, ROR-gamma) and chemokine receptors (CXCR3, CRTH2,
CCR6) and to assess expression of activation markers (CD69, CD154
and HLA-DR) in a cohort of CVID patients.
Objectives: PBMC (peripheral blood mononucler cells) were izolated
from whole peripheral blood using Ficoll-Paque gradient. After
isolation PBMC were stimulated with ionomycin and PMA (Phorbol
myristate acetate) for 6 hours. We measured expression and production
of CD3, CD4, CD8, CD69, CD154, HLA-DR, CXCR3, CRTH2,
CCR6, T-Bet, GATA-3, ROR-gamma, IFN-gamma, IL-5, IL-17 using
standard flowcytometric protocols for cell surface membrane and
intracellular markers and cytokine detection. All flowcytometric data
were statistically analyzed
Results: Together 20 CVID patients with/without autoimmune or
lymphoproliferative complications were analyzed. We compared the
results of CVID patients cohort to corresponding sex and age related
cohort of healthy controls. There are significant differences in the
intracellular cytokine production and expression of assessed markers
mentioned above.
Conclusions: We found skewing in the character of immune
response and in the expression of activation markers in our cohort
of CVID patients in comparison to healthy controls.