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Effects of interleukin 2 therapy on lymphocyte magnesium levels
Mark D McKee1, Stacey A Cecco, Julie E Niemela
1Surgery Branch, Clinical Pathology, and Biostatistics and Data Management Section, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA.
Abstract:
Interleukin 2 (IL-2) can cause partial or complete tumor regression in approximately 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 calcium 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 magnitude 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 function.
Insights
Interleukin 2 (IL-2) therapy for renal cell carcinoma depletes serum magnesium (Mg) but increases Mg within lymphocytes. This suggests Mg shifts may impact immune cell function during cancer treatment.
Area of Science:
- Oncology
- Immunology
- Biochemistry
Background:
- Interleukin 2 (IL-2) therapy can induce tumor regression in renal cell carcinoma patients.
- IL-2 treatment is associated with decreased serum and urinary levels of magnesium (Mg) and calcium.
- The impact of IL-2 on intracellular Mg levels, particularly in immune cells, remains less understood.
Purpose of the Study:
- To investigate the effect of IL-2 on lymphocyte magnesium (Mg) levels in patients with metastatic renal cell carcinoma.
- To compare Mg level changes across different IL-2 dosing regimens (high-dose IV, low-dose IV, subcutaneous).
Main Methods:
- Twenty-eight patients with metastatic renal cell carcinoma received IL-2 therapy.
- Serum ionized Mg, urinary Mg, and peripheral blood mononuclear cell (PBMC) Mg content were measured.
- Measurements were taken during IL-2 treatment and compared to baseline levels.
Main Results:
- Serum and ionized Mg levels significantly decreased within 12 hours of IL-2 treatment across all regimens.
- Urinary Mg excretion decreased in parallel with serum Mg levels.
- Peripheral blood mononuclear cell Mg content per cell significantly increased within 24 hours of IL-2 treatment.
Conclusions:
- IL-2 therapy leads to a concurrent decrease in serum Mg and an increase in lymphocyte Mg content.
- These Mg shifts occur regardless of the IL-2 administration route or dose intensity.
- Changes in Mg availability may influence lymphocyte proliferation and integrin function during IL-2 therapy.