high-dose intravenous IL-2 therapy can cause partial or complete regression of RCC in approximately 20% of these patients. The incidence of durable and complete regressions has led the US Food and Drug Administra- tion to approve IL-2 for the treatment of these patients. 2 The treatment-related toxicities of high-dose IL-2 include effects on the cardiovascular, pulmonary, hepat- ic, renal, hematologic, and central nervous systems and are completely reversible after the cessation of thera- py. 3-9 Recently, clinical trials for patients with RCC using intravenous and subcutaneous IL-2 treatment have been designed to minimize the risk of serious IL- 2 toxicity. These regimens have led to tumor regression in 6% to 33% of patients, although the relative effi- atients with metastatic RCC have a median sur- vival of 2 to 13 months and overall 2-year sur- vival rates of less than 25%. 1 Treatment with Effects of interleukin 2 therapy on lymphocyte magnesium levels MARK D. MCKEE, STACEY A. CECCO, JULIE E. NIEMELA, JANICE CORMIER, CHRISTINA J. KIM, SETH M. STEINBERG, NADJA N. REHAK, RONALD J. ELIN, and STEVEN A. ROSENBERG BETHESDA, MARYLAND Interleukin 2 (IL-2) can cause partial or complete tumor regression in approximate- ly 20% of patients with renal cell carcinoma. Among the many physiologic effects of IL-2, decreased serum levels of the divalent cations magnesium (Mg) and cal- cium have been demonstrated, with corresponding decreases in their urinary excretion. We investigated the effect of IL-2 on lymphocyte Mg levels among patients receiving three different dosing regimens. Twenty-eight patients with metastatic renal cell carcinoma were treated with high-dose intravenous, low- dose intravenous, or subcutaneous IL-2 therapy. Serum ionized Mg, urinary Mg, and peripheral blood mononuclear cell Mg levels were measured in samples from patients during treatment and compared with pretreatment levels. Serum Mg and ionized Mg levels decreased for all patients within 12 hours of treatment (P < .005) and remained low for the duration of therapy. Urinary Mg decreased in parallel with serum levels in all patients (P < .005). The peripheral blood mononuclear cell Mg content per cell increased within 24 hours of treatment (P < .005). The magni- tude of these changes was similar during the first week of treatment for patients receiving intravenous or subcutaneous administration of IL-2. During IL-2 therapy, lymphocyte Mg increases coincident with serum Mg depletion. Mg availability may have functional implications for lymphocyte proliferation and integrin func- tion. (J Lab Clin Med 2002;139:5-12) Abbreviations: IL-2 = interleukin 2; iMg = ionized magnesium; Mg = magnesium; PBMC = peripheral blood mononuclear cell; RBC = red blood cell; RCC = renal cell carcinoma; WBC = white blood cell 5 From the Surgery Branch, Clinical Pathology, and Biostatistics and Data Management Section, National Cancer Institute, National Insti- tutes of Health, Bethesda. Submitted January 8, 2001; revision submitted September 17, 2001; accepted September 24, 2001. Reprint requests: Mark D. McKee, Biological Sciences Division, Uni- versity of Chicago, 5841 South Maryland Ave, MC 5094, Chicago, IL 60637. 5/1/120361 doi:10.1067/mlc.2002.120361 P ORIGINAL ARTICLES