Abstract
Tofacitinib (Tofa) is an inhibitor of Janus Kinase 3, developed for the treatment of autoimmune diseases and for the prevention of transplant rejection. Due to its selective action on proliferating cells, Tofa can offer a way to block T cell activation, without toxic effects on resting cells. However, few studies have investigated the effects of Tofa on lymphocyte activation in vitro. Our aim was to study the action of Tofa on different lymphocyte subsets after in vitro stimulation and to track the behaviour of treated cells after interruption of the treatment. Peripheral blood lymphocytes were stimulated in vitro with mitogen and treated with two concentrations of Tofa. After a first period in culture, cells were washed and further incubated for an additional time. Lymphocyte subsets, activation phenotype and proliferation were assessed at the different time frames. As expected, Tofa was able to reduce the activation and proliferation of lymphocytes in the first four days of treatment. In addition the drug led to a relative decrease of Natural Killer, B cells and CD8 T cells compared to CD4 T cells. However, treated cells were still viable after the first period in culture and begun to proliferate, strikingly, in a dose dependent manner when the drug was removed from the environment by replacing the culture medium. This novel data does not necessarily predict a similar behaviour in vivo, but can warn about the clinical use of this drug when a discontinuation of treatment with Tofa is considered for any reason.
| Original language | English |
|---|---|
| Article number | e85463 |
| Journal | PLoS One |
| Volume | 9 |
| Issue number | 1 |
| DOIs | |
| Publication status | Published - Jan 9 2014 |
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ASJC Scopus subject areas
- Biochemistry, Genetics and Molecular Biology(all)
- Medicine(all)
- Agricultural and Biological Sciences(all)
Cite this
Fate of lymphocytes after withdrawal of tofacitinib treatment. / Piscianz, Elisa; Valencic, Erica; Cuzzoni, Eva; De Iudicibus, Sara; De Lorenzo, Elisa; Decorti, Giuliana; Tommasini, Alberto.
In: PLoS One, Vol. 9, No. 1, e85463, 09.01.2014.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Fate of lymphocytes after withdrawal of tofacitinib treatment
AU - Piscianz, Elisa
AU - Valencic, Erica
AU - Cuzzoni, Eva
AU - De Iudicibus, Sara
AU - De Lorenzo, Elisa
AU - Decorti, Giuliana
AU - Tommasini, Alberto
PY - 2014/1/9
Y1 - 2014/1/9
N2 - Tofacitinib (Tofa) is an inhibitor of Janus Kinase 3, developed for the treatment of autoimmune diseases and for the prevention of transplant rejection. Due to its selective action on proliferating cells, Tofa can offer a way to block T cell activation, without toxic effects on resting cells. However, few studies have investigated the effects of Tofa on lymphocyte activation in vitro. Our aim was to study the action of Tofa on different lymphocyte subsets after in vitro stimulation and to track the behaviour of treated cells after interruption of the treatment. Peripheral blood lymphocytes were stimulated in vitro with mitogen and treated with two concentrations of Tofa. After a first period in culture, cells were washed and further incubated for an additional time. Lymphocyte subsets, activation phenotype and proliferation were assessed at the different time frames. As expected, Tofa was able to reduce the activation and proliferation of lymphocytes in the first four days of treatment. In addition the drug led to a relative decrease of Natural Killer, B cells and CD8 T cells compared to CD4 T cells. However, treated cells were still viable after the first period in culture and begun to proliferate, strikingly, in a dose dependent manner when the drug was removed from the environment by replacing the culture medium. This novel data does not necessarily predict a similar behaviour in vivo, but can warn about the clinical use of this drug when a discontinuation of treatment with Tofa is considered for any reason.
AB - Tofacitinib (Tofa) is an inhibitor of Janus Kinase 3, developed for the treatment of autoimmune diseases and for the prevention of transplant rejection. Due to its selective action on proliferating cells, Tofa can offer a way to block T cell activation, without toxic effects on resting cells. However, few studies have investigated the effects of Tofa on lymphocyte activation in vitro. Our aim was to study the action of Tofa on different lymphocyte subsets after in vitro stimulation and to track the behaviour of treated cells after interruption of the treatment. Peripheral blood lymphocytes were stimulated in vitro with mitogen and treated with two concentrations of Tofa. After a first period in culture, cells were washed and further incubated for an additional time. Lymphocyte subsets, activation phenotype and proliferation were assessed at the different time frames. As expected, Tofa was able to reduce the activation and proliferation of lymphocytes in the first four days of treatment. In addition the drug led to a relative decrease of Natural Killer, B cells and CD8 T cells compared to CD4 T cells. However, treated cells were still viable after the first period in culture and begun to proliferate, strikingly, in a dose dependent manner when the drug was removed from the environment by replacing the culture medium. This novel data does not necessarily predict a similar behaviour in vivo, but can warn about the clinical use of this drug when a discontinuation of treatment with Tofa is considered for any reason.
UR - http://www.scopus.com/inward/record.url?scp=84897384127&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84897384127&partnerID=8YFLogxK
U2 - 10.1371/journal.pone.0085463
DO - 10.1371/journal.pone.0085463
M3 - Article
C2 - 24416411
AN - SCOPUS:84897384127
VL - 9
JO - PLoS One
JF - PLoS One
SN - 1932-6203
IS - 1
M1 - e85463
ER -