Cladribine inhibits secretion of pro-inflammatory cytokines and phagocytosis in human monocyte-derived M1 macrophages in-vitro.

Abstract:

:Cladribine (Cd) is a purine nucleoside analogue which in an oral formulation is approved for treatment of patients with multiple sclerosis (MS). It is known to mediate the effect through a short-term selective reduction of lymphocytes with minimal effect on the innate immune system. However, a few studies have emerged, that also demonstrate a beneficial immunomodulatory effect of cladribine on monocyte-derived cells. As cladribine crosses the blood-brain barrier this effect could have clinical meaningful impact in the treatment of MS, where recruitment of innate cells such as M1 macrophages play a role in plaque development. Here, we investigated the in-vitro effect on monocyte differentiation into M1 and M2 macrophages and dendritic cells as well as the effect on activation of M1 macrophages. In our experiments, cladribine in therapeutic relevant in-vitro concentrations, did not lead to apoptosis in differentiated M1, M2 macrophages or DCs and did not interfere with the phenotype of these differentiated cells. In M1 macrophages, cladribine reduced the secretion of IL-6 and TNF-α observed after activation with LPS. Similar, cladribine reduced the phagocytic capacity of LPS activated M1 macrophages but did not affect unactivated cells. We conclude, that such reduction of inflammatory potential as well as reduced M1 phagocytic activity, e.g. within an MS plaque, could be an additional clinical meaningful effect of cladribine in the treatment of MS while at the same time it would leave M1 macrophages intact for the protection against infections.

journal_name

Int Immunopharmacol

authors

Mathiesen CBK,Rudjord-Levann AM,Gad M,Larsen J,Sellebjerg F,Pedersen AE

doi

10.1016/j.intimp.2020.107270

subject

Has Abstract

pub_date

2021-02-01 00:00:00

pages

107270

eissn

1567-5769

issn

1878-1705

pii

S1567-5769(20)33737-1

journal_volume

91

pub_type

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