ABSTRACT
BACKGROUND: Cladribine causes sustained reduction in peripheral T and B cell populations while sparing other immune cells. We determined two populations of dendritic cells (DCs): namely CD1c(+)/CD19(-) (myeloid DCs) and CD303(+)/CD123(+) (plasmacytoid DCs), CD19(+) B lymphocytes, CD3(+) T lymphocytes and CD4(+) or CD8(+) subpopulations in patients with multiple sclerosis after cladribine therapy. METHODS: We examined 50 patients with secondary progressive multiple sclerosis (SP MS) according to McDonalds et al.'s criteria, 2001 [15]. Blood samples were collected before the initiation of cladribine therapy and after 1st, 2nd, 3th, 4th and 5th courses of treatment. DC subsets, T and B cells were analyzed by flow cytometry. RESULTS: During cladribine treatment the myeloid DCs CD1c(+)/CD19(-) did not change (p=0.73175), and the plasmacytoid DCs CD303(+)/CD123(+) significantly increased (p=0.00034) which resulted in significant changes in the ratio of myeloid DCs to plasmacytoid DCs (p=0.00273). During therapy, B lymphocyte CD19(+) significantly decreased (p=0.00005) and significant changes in CD4(+) cells (p=0.00191), changes in CD8(+) cells (p=0.05760) and significant changes in CD3(+) (p=0.01822) were found. CONCLUSIONS: We noticed significant trend to increase the CD303(+) circulating the dendritic cells. This population produces large amounts of IFN-alfa. We found significant and rapid decrease in B cells and CD4(+) Th cells. Our results suggest two possible ways of beneficial cladribine influence on immune system in MS. Induction of IFN-alfa producing cells and their predominance over BDCA-1(+) DCs, which are associated with cytotoxic response. Additionally, cladribine could influence two populations of lymphocytes: B cells and Th lymphocytes responsible for induction of immune response against myelin antigens.
Subject(s)
B-Lymphocytes/drug effects , Cladribine/pharmacology , Dendritic Cells/drug effects , Immunosuppressive Agents/pharmacology , Multiple Sclerosis/pathology , T-Lymphocytes/drug effects , Adult , Analysis of Variance , Antigens, CD/metabolism , Cladribine/therapeutic use , Female , Flow Cytometry , Humans , Immunosuppressive Agents/therapeutic use , Male , Middle Aged , Multiple Sclerosis/drug therapy , Multiple Sclerosis/immunologyABSTRACT
Oxidative stress is an imbalance between free radicals production and antioxidant defences. Reactive oxygen species (ROS) and reactive nitrogen species (RNS) can attact and demage a variety of critical biological molecules, including lipids, essential cellular proteins and DNA and may be exert in pathogenesis of many disorders. Products of lipid peroxidation can be easily reliably detected in biological fluids and tissues, yielding sensitive and specific signals of lipid peroxidation occurred in vivo. Those products are: isoprostanes (isoP) dimalonealdehyde (MDA), 4-hydroxynonenal (4-HNE). Paraoxonase-1 (PON-1) play a key role in defence of lipid peroxidation. PON-1 is an serum enzyme bound up with high density lipoproteins (HDL). The aim of this work is to discuss the role of oxidative stress in the pathogenesis of multiple sclerosis.
