Cheever M A, Thompson J A, Kern D E, Greenberg P D
J Immunol. 1985 Jun;134(6):3895-900.
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.
评估了白细胞介素2（IL 2）给药途径和频率对其在体内诱导活化T细胞生长能力的影响。初步药代动力学研究证实，静脉注射IL 2会导致血清浓度相对较高的峰值，但血清半衰期较短。相比之下，腹腔内或皮下注射IL 2会导致较低的峰值浓度，但血清半衰期延长。通过测量先前用IL 2长期培养的过继转移T细胞在体内的生长情况，评估了通过这些途径给药的IL 2的生物利用度，因为已证明此类细胞在体内的生长与所给药的IL 2剂量成正比。结果表明，腹腔内、皮下或静脉注射IL 2均可在体内显著促进供体T细胞生长。因此，IL 2可在注射部位以外的远处发挥体内作用。此外，体内T细胞生长的程度因IL 2给药途径而异，并且与血清中可检测到IL 2的时间长度相关，而非与所达到的峰值水平相关（即静脉注射的IL 2峰值浓度最高，但效果最差）。正如这些发现所表明的，将IL 2的总剂量分成频繁的低剂量注射比将IL 2的总剂量分成较少频率的高剂量注射在体内诱导T细胞生长方面更有效。这些研究证实了IL 2在体内诱导活化T细胞生长的巨大潜力，并表明T细胞生长速率不仅反映剂量，还反映IL 2给药的途径和时间。
