Kinetics of W3/25 anti-rat CD4 monoclonal antibody. Studies on optimal doses and time-related effects.
Although anti-CD4 monoclonal antibodies (MoAb) have been proven successful in preventing or treating adjuvant arthritis, little is known about the duration of the effects of these MoAb and their pharmacokinetics. In this work, we report the effects of a mouse anti-rat CD4 MoAb, named W3/25, on peripheral blood lymphocytes from female Wistar rats. Animals received a single dose of W3/25, from 1 to 3 mg, and blood was sampled at different time points from 0 h to 15 days after MoAb administration. After erythrocyte lysis, samples were stained by indirect immunofluorescence and analyzed by flow cytometry. Pharmacokinetic data were studied by assessing plasma levels of mouse IgG1 by ELISA-sandwich. W3/25 produced the down-regulation of surface CD4 molecule as early as 20 min after its administration at doses of 2 and 3 mg. The same effect was seen 30 min after a dose of 1 mg. The recovery of lymphocytes with normal expression of CD4 also depended of the dose administered. Thus, CD4+ lymphocytes were recovered at 48, 72 and 96 h in rats treated with 1, 2 or 3 mg of W3/25, respectively. Plasma levels of free antibody were detectable from 20 min to 72 h, 60 min to 48 h and 60 min to 24 h after administration of 3, 2 and 1 mg, respectively, of W3/25. The mouse IgG1 MoAb used in this study followed a two-compartment model and its behavior was linear.
Unit of Physiology, Faculty of Pharmacy, University of Barcelona, Spain.
F
F
Caballero
C
C
Pelegrí
M
M
Castell
A
A
Franch
C
C
Castellote
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology*; D015704:CD4 Antigens / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000502:physiology; D018414:CD8-Positive T-Lymphocytes / Q000502:physiology; D004306:Dose-Response Relationship, Immunologic; D005260:Female; D007074:Immunoglobulin G / Q000097:blood / Q000145:classification; D007700:Kinetics; D051379:Mice; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors
D000911:Antibodies, Monoclonal; D015704:CD4 Antigens; D007074:Immunoglobulin G