Influence of FK 506 (tacrolimus) on circulating CD4+ T cells expressing CD25 and CD45RA antigens in 19 patients with chronic progressive multiple sclerosis participating in an open label drug safety trial.
We have taken the opportunity of a clinical trial of the potential efficacy and safety of FK 506 (tacrolimus) in chronic progressive multiple sclerosis (MS) to examine the influence of this potent new immunosuppressant on circulating T-lymphocytes in an otherwise healthy non-transplant population. Peripheral blood levels of subsets of CD4+ T lymphocytes expressing the activation molecule interleukin-2 receptor (p55 alpha chain; CD25) or the CD45RA isoform were determined sequentially in 19 patients that were treated continuously with oral FK 506 (starting dose 0.15 mg/kg/day) for 12 months. No significant change in the proportion of circulating CD25+ CD4+ cells was observed over the study period in which the mean trough plasma FK 506 level rose from 0.3 +/- 0.2 to 0.5 +/- 0.4 ng/ml. There was also no significant effect of FK 506 on the percentage of CD45R+ CD4+ cells in the peripheral blood at 12 months compared with pretreatment values. Analysis of a subgroup of 7 patients, who showed a sustained reduction in CD25+ CD4+ cells and a reciprocal increase in CD45RA+ CD4+ cells for at least 6 months after start of treatment, did not reveal any difference in disability at one year compared with the treatment group as a whole. The side effects of FK 506 were mild and the overall degree of disability estimated by the mean Kurtzke expanded disability status scale (EDSS) score or the ambulation index did not deteriorate significantly in the 19 patients studied over the 12 months of FK 506 administration.
Lemster
B
B
Autoimmune Clinic, University of Pittsburgh Medical Center 15213, USA.
Huang
L L
LL
Irish
W
W
Woo
J
J
Carroll
P B
PB
Abu-Elmagd
K
K
Rilo
H R
HR
Johnson
N
N
Russell-Hall
R
R
Fung
J J
JJ
D000284:Administration, Oral; D000328:Adult; D000368:Aged; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D005221:Fatigue / Q000139:chemically induced; D001068:Feeding and Eating Disorders / Q000139:chemically induced; D005260:Female; D006801:Humans; D017493:Leukocyte Common Antigens / Q000032:analysis*; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000097:blood / Q000188:drug therapy* / Q000276:immunology; D010865:Pilot Projects; D015375:Receptors, Interleukin-2 / Q000032:analysis*; D016559:Tacrolimus / Q000009:adverse effects / Q000097:blood / Q000494:pharmacology*; D014202:Tremor / Q000139:chemically induced
D015375:Receptors, Interleukin-2; D017493:Leukocyte Common Antigens; D016559:Tacrolimus