Lymphocyte subpopulations, oxidative burst and apoptosis in peripheral blood cells of patients with multiple sclerosis-effect of interferon-beta.
At present, the most efficient therapeutical treatment of multiple sclerosis (MS) is achieved by IFN-beta. However, its in vivo effects remain incompletely understood. If applied parenterally, the hydrophobic IFN-beta acts primarily on blood cells with probable selectivity for functionally different lymphocyte subpopulations, monocytes and granulocytes. We have investigated the expression of the activation marker interleukin-2 receptor-alpha (CD25) on CD3+ T cells, CD19+ B cells, foetal-type gamma(delta)+CD3+ T cells and foetal-type CD5+CD19+ B cells of the peripheral blood. In addition, the oxidative burst activity and apoptosis have been determined in mononuclear and polymorphonuclear blood cells, respectively. The study accompanied a phase III trial with IFN-beta1b (BETAFERON, Schering). Two groups of MS patients with relapsing-remitting course of the disease have been investigated at 8 time points (days 0, 5, 15, 31, 60, 90, 180 and 270 after starting therapy): (1) verum group (n = 8) with application of 8 Mill. units IFN-beta1 b every other day, and (2) placebo group (n = 4) with application of placebo for 3 months and therapy as in (1) from day 90 onward. The main results were: (1) Activated T cells decreased until day 180 in the verum group and return thereafter to pre-treatment values, whereas in the placebo group the values remained relatively stable over the whole observation period. (2) Activated B cells increased between days 90 and 270 in both groups, i.e. after verum application in both groups. (3) Foetal-type B cells were more activated than total B and T cells with increase over time in both groups. (4) Foetal-type T cells exerted relatively stable intra-individual levels with generally low CD25 expression, but punctual CD25 peaks in both groups. (5) The spontaneous oxidative burst was higher in lymphocytes, more variable in monocytes and faster increasing in granulocytes in the verum group than in the placebo group. (6) Apoptosis of mononuclear cells and granulocytes showed similar variations in the verum and placebo groups with the exception of a selective increase over time of the proportion of granulocytes undergoing induced apoptosis in the verum group. It is concluded that IFN-beta has the following main effects on the immune system of MS patients: (1) the T cell immunity is systemically and reversibly suppressed, (2) the foetal-type lymphocytes, which are responsible for the first line of defence of infections, are stimulated in the long range, (3) the oxidative burst activity is increased in lymphocytes and granulocytes and instable in monocytes, and (4) the inducibility of apoptosis in granulocytes is increased. Re-examination of the altered blood cell parameters after long-term IFN-beta therapy is warranted.
Mix
Eilhard
E
Department of Neurology, University of Rostock, Gehlsheimer Str. 20, P.O. Box 100888, 18055 Rostock, Germany. eilhard.mix@med.uni-rostock.de
Stefan
Katja
K
Höppner
Jaqueline
J
Klauer
Thomas
T
Zettl
Uwe K
UK
Strauss
Ulf
U
Meyer-Rienecker
Hans-J
HJ
Rolfs
Arndt
A
D000328:Adult; D000911:Antibodies, Monoclonal; D017209:Apoptosis / Q000187:drug effects; D001402:B-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D002478:Cells, Cultured; D005260:Female; D005434:Flow Cytometry; D006098:Granulocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D006801:Humans; D020287:In Situ Nick-End Labeling; D000068576:Interferon beta-1b; D016899:Interferon-beta / Q000276:immunology / Q000627:therapeutic use*; D007962:Leukocytes / Q000166:cytology / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D016131:Lymphocyte Subsets / Q000166:cytology / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D008297:Male; D009000:Monocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D009103:Multiple Sclerosis / Q000097:blood / Q000188:drug therapy* / Q000276:immunology*; D016897:Respiratory Burst / Q000187:drug effects; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology / Q000378:metabolism
D000911:Antibodies, Monoclonal; D000068576:Interferon beta-1b; D016899:Interferon-beta