Effects of IFN-beta, leptin and simvastatin on LIF secretion by T lymphocytes of MS patients and healthy controls.
In multiple sclerosis (MS), oligodendrocyte injury is believed to be caused by an aberrant immune response initiated by autoreactive T cells. Increasing evidence indicates that inflammatory responses in the central nervous system are not exclusively detrimental, but may also exert protective effects. Such protective effects are potentially mediated by the local secretion of neurotrophic factors by immune cells. We previously reported that T cells and monocytes in vitro and in inflammatory MS lesions produce leukaemia inhibitory factor (LIF), a member of the neuropoietic family of neurotrophins. In the present study, we report a reduced LIF production by CD4+ T cells of relapsing remitting MS patients as compared to healthy controls. Furthermore, immunomodulatory agents such as leptin, IFN-beta and simvastatin were studied for their potential to alter LIF and secretion of other cytokines by T cells and monocytes of relapsing remitting MS patients and healthy controls. Low doses of simvastatin, but not IFN-beta or leptin enhanced LIF secretion by CD4+ T cells of RR-MS patients. We further demonstrated that LIF did not influence viability, proliferation and cytokine secretion of T cells. Together these data provide new information on the regulation of LIF secretion by immune cells. Further insights into the complex regulation of neurotrophic factors such as LIF may prove useful for treatment of MS.
Vanderlocht
Joris
J
Hasselt University, Biomedical Research Institute and Transnational Universiteit Limburg, School of Life Sciences, Diepenbeek, Belgium.
Hendriks
Jerome J A
JJ
Venken
Koen
K
Stinissen
Piet
P
Hellings
Niels
N
D000328:Adult; D000368:Aged; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D002478:Cells, Cultured; D016207:Cytokines / Q000187:drug effects / Q000378:metabolism; D019610:Cytoprotection / Q000187:drug effects / Q000276:immunology; D015536:Down-Regulation / Q000187:drug effects / Q000276:immunology; D005260:Female; D006801:Humans; D016899:Interferon-beta / Q000494:pharmacology*; D015850:Interleukin-6 / Q000378:metabolism*; D020738:Leptin / Q000494:pharmacology*; D053605:Leukemia Inhibitory Factor; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000097:blood / Q000276:immunology*; D018696:Neuroprotective Agents / Q000276:immunology / Q000494:pharmacology; D012016:Reference Values; D019821:Simvastatin / Q000494:pharmacology*; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects / Q000276:immunology
D016207:Cytokines; D015850:Interleukin-6; C507837:LIF protein, human; D020738:Leptin; D053605:Leukemia Inhibitory Factor; D018696:Neuroprotective Agents; D016899:Interferon-beta; D019821:Simvastatin