Affiliation:
1. Laboratory of Applied Molecular Biology and Immunology, W0414100, University of Tlemcen, 13000 Tlemcen, Algeria
Abstract
Background:
Monocytes are the main blood innate mononuclear phagocyte and one of the
most important effector cells expressing Fcγ receptor, which is critical for the interaction with Fc domain
of antibodies.
Objective:
To evaluate the effect of Rituximab (RTX, a chimeric human anti-CD20 monoclonal antibody)
on the functional activities of Monocytes (MOs) at the onset of human Type 1 Diabetes (T1D).
Methods:
MOs were isolated from peripheral blood mononuclear cells (PBMCs) obtained from volunteer
patients with recent-onset T1D and healthy control donors.
Results:
The levels of the production of Interleukin 1β (IL-1β) and IL-6 were significantly increased in
MOs from patients with T1D when compared to MOs from healthy controls (respectively, p < 0.01 and
p < 0.05). Similarly, Interferon γ (IFN-γ), and intracellular free Calcium Ion (ifCa2+) levels were increased
in T1D MOs than in control MOs, but the difference did not reach a significant level. Conversely,
the production levels of IL-4 and catalase activity, as well as of both phagocytosis and killing
capacities were decreased in MOs of T1D patients compared to MOs from healthy controls, but the
difference was not significant for catalase activity and killing capacity (respectively, p < 0.01, p > 0.05,
p < 0.01, and p > 0.05). Additionally, treatment with RTX significantly upregulated phagocytosis (p <
0.05), markedly downregulated the release of IL-1β (p < 0.01), ifCa2+, hydrogen peroxide (H2O2), and
slightly downregulated the Nitric Oxide Synthase (NOS) activity, NOS activity-to-arginase activity
ratio, the levels of Lactate Dehydrogenase (LDH)-based cytotoxicity, and the production of IL-6 and
IFN-γ. Moreover, RTX treatment significantly upregulated the production of IL-4 (p < 0.05), IL-10
(p < 0.01) and the catalase activity (p < 0.05).
Conclusion:
Our study has shown for the first time that RTX can reverse the abnormal functional activities
of MOs as well as their production of proinflammatory cytokines at the onset of T1D. From a
therapeutic point of view, RTX may potentially be suggested at the beginning of T1D to immunomodulate
innate immunity and inflammatory conditions.
Publisher
Bentham Science Publishers Ltd.
Subject
Immunology and Allergy,Endocrinology, Diabetes and Metabolism
Cited by
6 articles.
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