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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.

We previously found an inverse correlation between platelet ionized magnesium concentration ((Mg2+)i) and serum total cholesterol concentration in normal male but not female subjects. In the present study, we determined the platelet (Mg2+)i by using a fluorescent ionized magnesium (Mg2+) indicator, FURAPTRA, and measured the serum concentrations of the following: total cholesterol; very-low-density lipoprotein cholesterol (VLDL-C); low-density lipoprotein cholesterol (LDL-C); high-density lipoprotein cholesterol (HDL-C); antioxidized low-density lipoprotein (LDL) autoantibodies; lipoprotein(a); apolipoproteins A-I (apo A-I) and B (apo B); triglycerides; estradiol-17 (E2); ceruloplasmin (Cp); and selected electrolytes, including total and ionized magnesium and calcium and total protein and albumin. In men, but not in women, platelet (Mg2+)i significantly inversely correlated with serum total cholesterol (r = -0.52, p < 0.02), LDL-C (r = -0.54, p < 0.009 by a "direct" method; r = -0.40, p < 0.05 by an electrophoretic method), and apo B (r = -0.42, p < 0.04). We found no significant correlations between platelet (Mg2+)i and any other variables, including serum total and ionized magnesium, antioxidized LDL autoantibodies, Cp, and E2. We speculate that decreased platelet (Mg2+)i is a possible marker for platelet membrane alterations that may affect platelet involvement in thrombosis and atherogenesis.

The current laboratory approach to assessing magnesium status is based on determining the concentration of total Mg ((Mg)) in serum or plasma. This strategy is problematic in that the amount of Mg in blood is less than 1% of total body Mg and does not accurately reflect (Mg) in other tissues. Furthermore, the (Mg) of blood does not distinguish biologically active, ionized Mg from the bound fraction. The goal of this study was to determine intracellular ionized Mg ((Mg++)i) of skeletal muscle in vivo and to compare results with the (Mg) of blood constituents. (Mg++)i was determined in resting skeletal muscle by using phosphorus 31 magnetic resonance (31P-MR) spectroscopy. (Mg) was measured in serum (S(Mg)), serum ultrafiltrate (UF(Mg)), mononuclear blood cells (MBC(Mg)), and red blood cells (RBC(Mg)) by using atomic absorption spectroscopy or a colorimetric assay. In a sample of 60 healthy adult subjects, skeletal muscle (Mg++)i = 557 +/- 97 mumol/L (mean +/- SD); S(Mg) = 0.78 +/- 0.09 mmol/L; UF(Mg) = 0.60 +/- 0.12 mmol/L; MBC(Mg) = 13.8 +/- 2.3 mmol/L; and, RBC(Mg) = 1.92 +/- 0.33 mmol/L. A significant negative correlation was found between (Mg++)i and S(Mg) (r = -0.43, p < 0.05). S(Mg) was significantly lower (p < 0.05) and (Mg++)i significantly higher (p < 0.05) in women than in men, but neither was related to age. These findings provide new insight into the relationship between blood Mg measures and (Mg++)i of the largest soft tissue mass of the human body.

In vitro von Willebrand factor is released from endothelial cells by a variety of stimuli. These studies have provided information on the synthesis, multimeric organization, sites of storage, and release of von Willebrand factor. We have administered endotoxin (Escherichia coli, 4 ng/kg) intravenously to 11 normal volunteers and have followed changes in levels of factor VIII, von Willebrand factor antigen, von Willebrand factor activity (ristocetin cofactor assay), and the multimeric organization of von Willebrand factor. Within 2 hours after injection, the levels of factor VIII, von Willebrand factor antigen, and von Willebrand factor activity rose significantly compared with the preinjection values (p less than 0.001, p less than 0.005, and p less than 0.001, respectively). The levels peaked 4 to 6 hours after the endotoxin injection. The mean peak values of von Willebrand factor antigen and activity were 4.67 microns/ml and 4.62 microns/ml, respectively. The factor VIII level rose to a mean of 2.87 microns/ml. Forty-eight hours after the administration of endotoxin, the von Willebrand factor antigen and activity levels remained significantly elevated (2.62 micrograms/ml and 2.20 microns/ml, respectively), but by 24 hours, the factor VIII level was not significantly elevated (1.47 microns/ml). After endotoxin administration, the agarose gel electrophoresis of von Willebrand factor demonstrated an increase in the largest von Willebrand factor multimers normally present and the appearance of von Willebrand factor multimers larger than those normally present in plasma. The largest von Willebrand factor multimers were present for 2 to 4 hours after the administration of endotoxin.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood concentrations of six acute phase reactants (ESR, neutrophil count, fibrinogen, haptoglobin, alpha 1-antitrypsin, and ferritin), parameters of muscle necrosis (myoglobin, CK, ALT, and AST) as well as hemopexin, iron, and TIBC were determined before and for 7 consecutive days after muscle biopsy in patients and in a control group. A muscle biopsy was chosen as a standardized surgical procedure that induces a mild transient inflammatory response. After muscle biopsy, a significant increase occurred in five (ESR, neutrophil count, fibrinogen, haptoglobin, and alpha 1-antitrypsin) of the six acute phase reactants. The concentration of serum ferritin did not show a significant change. A significant decrease was noted in the serum iron concentration and a significant increase occurred with CK and myoglobin secondary to the muscle biopsy. Thus the inflammation of a muscle biopsy produces a significant acute phase reaction.

Magnesium deficiency in rats causes anemia, the mechanism of which is unknown. The effect of dietary magnesium, splenectomy, and magnesium content of erythrocytes on erythrocyte survival was studied in Fisher rats. Half of the animals were splenectomized, the remainder sham-splenectomized; each group was subdivided, and some were placed on a magnesium-deficient diet, the rest on a control diet. After 6 weeks, each of the four subgroups was divided, half were given 51Cr-labeled red cells from magnesium-deficient rats, the remainder, labeled normal red cells. The survival functions of the labeled erythrocytes were fitted to a mathematical model composed of both first-order and accelerating components. The results show that the most important factor influencing erythrocyte survival was dietary magnesium intake. The magnesium content of the transfused red cells affected erythrocyte survival only in the rats fed the control diet, whereas splenectomy affected erythrocyte survival only in rats receiving the magnesium-deficient diet. The accelerating component of the survival function was increased eightfold in the animals fed the magnesium-deficient diet, whereas much smaller changes occurred in the first-order components.