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Effect of commercial peritoneal dialysis fluids on the lytic function of lymphokine-activated killer cells
A L Moore1, B W Grant, J A Dorighi
1Vermont Regional Cancer Center, Burlington.
Intraperitoneal (ip) immunotherapies are often administered in saline or peritoneal dialysis solutions. In preparation for a Phase I i.p. interleukin-2/lymphokine-activated killer cell (IL-2/LAK) trial in patients with recurrent ovarian cancer, we evaluated the effect of six solutions, including two 1.5% dextrose peritoneal dialysis solutions (PDS), on the lytic function of LAK. In vitro IL-2-activated LAK cells were exposed to solutions, washed with Hanks' balanced salt solution, and lytic activity was measured in a standard 4-h chromium release assay using Daudi as a tumor target. LAK function was abrogated after 2 h of exposure to Inpersol and after only 20 min of exposure to Dianeal PD-2. Five percent dextrose also significantly decreased lytic capabilities of LAK, whereas 0.9% sodium chloride or lactated Ringers had no deleterious effect on function. Adjustment of PDS to pH greater than 6.5 decreased the damaging effect on LAK function, suggesting that the low pH of PDS and 5% dextrose results in a loss of LAK cell viability and therefore lytic function. Based on these data, we have chosen to administer IL-2/LAK i.p. in lactated Ringers.
Intraperitoneal (ip) immunotherapies are often administered in saline or peritoneal dialysis solutions. In preparation for a Phase I i.p. interleukin-2/lymphokine-activated killer cell (IL-2/LAK) trial in patients with recurrent ovarian cancer, we evaluated the effect of six solutions, including two 1.5% dextrose peritoneal dialysis solutions (PDS), on the lytic function of LAK. In vitro IL-2-activated LAK cells were exposed to solutions, washed with Hanks' balanced salt solution, and lytic activity was measured in a standard 4-h chromium release assay using Daudi as a tumor target. LAK function was abrogated after 2 h of exposure to Inpersol and after only 20 min of exposure to Dianeal PD-2. Five percent dextrose also significantly decreased lytic capabilities of LAK, whereas 0.9% sodium chloride or lactated Ringers had no deleterious effect on function. Adjustment of PDS to pH greater than 6.5 decreased the damaging effect on LAK function, suggesting that the low pH of PDS and 5% dextrose results in a loss of LAK cell viability and therefore lytic function. Based on these data, we have chosen to administer IL-2/LAK i.p. in lactated Ringers.