PT - JOURNAL ARTICLE AU - Tom J. Parry AU - Todd A. Riccobene AU - Steven J. Strawn AU - Rita Williams AU - Rami Daoud AU - Jeffrey Carrell AU - Svetlana Sosnovtseva AU - Renée C. Miceli AU - Carol M. Poortman AU - Les Sekut AU - Yuling Li AU - James Fikes AU - Cynthia Sung TI - Pharmacokinetics and Immunological Effects of Exogenously Administered Recombinant Human B Lymphocyte Stimulator (BLyS) in Mice DP - 2001 Feb 01 TA - Journal of Pharmacology and Experimental Therapeutics PG - 396--404 VI - 296 IP - 2 4099 - http://jpet.aspetjournals.org/content/296/2/396.short 4100 - http://jpet.aspetjournals.org/content/296/2/396.full SO - J Pharmacol Exp Ther2001 Feb 01; 296 AB - B lymphocyte stimulator (BLyS; also known as TNFSF20, BAFF, TALL-1, zTNF4, and THANK), a tumor necrosis factor ligand family member, has recently been identified as a factor that promotes expansion and differentiation of the B cell population, leading to increases in serum immunoglobulin levels. Here, pharmacokinetic parameters for BLyS administered i.v. and s.c. to mice are described, and the effects of different dosing regimens on serum and salivary immunoglobulin levels as well as splenic cell populations are reported. The pharmacokinetics of BLyS following i.v. injection are monophasic with a half-life of 160 min, a clearance of 0.22 ml/min-kg, and a volume of distribution of 53 ml/kg. Systemic administration of BLyS to mice resulted in increased serum IgG, IgA, IgM, and IgE and salivary IgA as well as splenic B cell population expansion and differentiation. The i.v. and s.c. routes of administration were pharmacologically equivalent, even though s.c. bioavailability of BLyS is only 25%. BLyS (s.c.) dramatically elevated serum IgG and IgA levels, and the duration of the responses after cessation of treatment (t 1/2 = 4.4 and 1.3 days, respectively) are similar to the half-lives of endogenous IgG and IgA in mice. The IgM response is more modest than that of IgG and IgA but lasts longer (t 1/2 = 7.0 days) than the half-life of endogenous IgM. A linear pharmacodynamic response was identified between days of dosing × log(dose), and increases in serum IgG, IgA, and IgM indicating that the response is more sensitive to the duration of dosing than to the cumulative dose. The implications of these findings for therapeutic administration of BLyS are discussed.