PMID- 3872906 OWN - NLM STAT- MEDLINE DCOM- 19850620 LR - 20071114 IS - 0022-1767 (Print) IS - 0022-1767 (Linking) VI - 134 IP - 6 DP - 1985 Jun TI - Interleukin 2 (IL 2) administered in vivo: influence of IL 2 route and timing on T cell growth. PG - 3895-900 AB - The influence of the route and the frequency of IL 2 administration on the ability of IL 2 to induce the growth of activated T cells in vivo was evaluated. Initial pharmacokinetic studies confirmed that i.v. injection of IL 2 results in a relatively high peak serum concentration, but a short serum half-life. By contrast, i.p. or subcutaneous (s.c.) injection of IL 2 results in a lower peak concentration but a prolonged serum half-life. The bioavailability of IL 2 administered by these routes was assessed by measuring the in vivo growth of adoptively transferred T cells that had been previously cultured long-term with IL 2, because the growth of such cells in vivo has been shown to be proportional to the dose of IL 2 administered. The results demonstrated that i.p., s.c., or i.v. administration of IL 2 each resulted in marked donor T cell growth in vivo. Thus, IL 2 can function in vivo at sites distant to the sites of injection. In addition, the magnitude of T cell growth in vivo varied dependent on the route of IL 2 administration and correlated with the length of time IL 2 was detectable in serum, rather than the peak level achieved (i.e., IL 2 inoculated i.v. had the highest peak concentration but was least effective). As suggested by these findings, dividing the total dose of IL 2 into frequent low-dose injections was more effective in inducing T cell growth in vivo than was dividing the total dose of IL 2 into less frequent higher-dose injections. These studies confirm the great potential for IL 2 to induce the growth of activated of T cells in vivo and demonstrate that the rate of T cell growth reflects not only the dose but also the route and timing of IL 2 administration. FAU - Cheever, M A AU - Cheever MA FAU - Thompson, J A AU - Thompson JA FAU - Kern, D E AU - Kern DE FAU - Greenberg, P D AU - Greenberg PD LA - eng GR - CA 00721/CA/NCI NIH HHS/United States GR - CA 30558/CA/NCI NIH HHS/United States GR - CA 33084/CA/NCI NIH HHS/United States PT - Comparative Study PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, P.H.S. PL - United States TA - J Immunol JT - Journal of immunology (Baltimore, Md. : 1950) JID - 2985117R RN - 0 (Interleukin-2) SB - IM MH - Animals MH - Cell Division MH - Dose-Response Relationship, Immunologic MH - Drug Administration Schedule MH - Injections, Intraperitoneal MH - Injections, Intravenous MH - Injections, Subcutaneous MH - Interleukin-2/*administration & dosage/physiology MH - Kinetics MH - *Lymphocyte Activation MH - Mice MH - Mice, Inbred C57BL MH - T-Lymphocytes/*cytology/immunology EDAT- 1985/06/01 00:00 MHDA- 1985/06/01 00:01 CRDT- 1985/06/01 00:00 PHST- 1985/06/01 00:00 [pubmed] PHST- 1985/06/01 00:01 [medline] PHST- 1985/06/01 00:00 [entrez] PST - ppublish SO - J Immunol. 1985 Jun;134(6):3895-900.