Cladribine impedes in vitro migration of mononuclear cells: a possible implication for treating multiple sclerosis.
BACKGROUND
Damage of the blood-brain barrier and the migration of immunocompetent cells into the CNS represent key events in the immunopathogenesis of multiple sclerosis (MS). Cladribine is an immunosuppressive drug currently investigated in a phase-III clinical trial for relapsing-remitting MS. However, its precise mode of action remains elusive so far.


METHODS
Peripheral blood mononuclear cells (PBMCs) were isolated from five patients with MS and five healthy donors. PBMCs were treated with cladribine in vitro. The migratory capacity was studied in an in vitro Boyden chamber assay; cells and their rate of migration were analyzed by light microscopy and flow cytometry.


RESULTS
Cladribine decreased the migratory capacity of CD14(+) monocytes, as well as of CD4(+) and CD8(+) T lymphocytes. T lymphocytes were affected more than monocytes. There was no difference in this effect when comparing mononuclear cells from MS patients with cells from healthy controls.


CONCLUSIONS
Cladribine might achieve, at least in part, its clinical and paraclinical efficacy by inhibiting the migration of inflammatory cells into and within the CNS.
Kopadze
T
T
Department of Neurology, Research Group for Clinical and Experimental Neuroimmunology, Heinrich-Heine University, Düsseldorf, Germany.
Döbert
M
M
Leussink
V I
VI
Dehmel
T
T
Kieseier
B C
BC
D000328:Adult; D015704:CD4 Antigens / Q000378:metabolism; D016827:CD8 Antigens / Q000378:metabolism; D002465:Cell Movement / Q000187:drug effects*; D017338:Cladribine / Q000494:pharmacology*; D005434:Flow Cytometry; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D007963:Leukocytes, Mononuclear / Q000187:drug effects* / Q000502:physiology; D018950:Lipopolysaccharide Receptors / Q000378:metabolism; D009000:Monocytes / Q000378:metabolism; D009103:Multiple Sclerosis / Q000188:drug therapy / Q000503:physiopathology; D010835:Phytohemagglutinins / Q000494:pharmacology; D013601:T-Lymphocytes / Q000378:metabolism
D015704:CD4 Antigens; D016827:CD8 Antigens; D007166:Immunosuppressive Agents; D018950:Lipopolysaccharide Receptors; D010835:Phytohemagglutinins; D017338:Cladribine