Biological activity of recombinant interleukin-2 in intravenous admixtures containing antibiotic, morphine sulfate, or total parenteral nutrient solution

The biological activity of recombinant interleukin-2 in intravenous admixtures containing gentamicin sulfate, tobramycin sulfate, amikacin sulfate, ticarcillin disodium, piperacillin sodium, morphine sulfate, or total parenteral nutrient (TPN) solution was investigated. Recombinant interleukin-2 in a formulation containing human serum albumin was diluted to a therapeutic dose and mixed with the other drugs in test tubes to simulate mixing distal to the Y-site of an i.v. administration set. All test tubes were visually observed for precipitates. Triplicate test samples of recombinant interleukin-2 and interleukin-2 with drug were added to microplate wells containing lymphocyte tissue culture media (an interleukin- 2-dependent murine cytotoxic T cell line, CTLL-2) using serial dilutions. The microplates were incubated then pulsed with mouse lymphocyte media containing tritiated thymidine (³H-thymidine). The amount of ³H-thymidine incorporated into lymphocyte DNA was measured using a beta counter. The average counts per minute (cpm) of a sample was analyzed as a function of the logarithm of sample dilution; one interleukin-2 unit was defined as 50% of the maximum cpm measured in the samples. At minimum dilutions, ticarcillin disodium reduced the effect of interleukin-2 on CTLL-2 growth; the other antibiotics and morphine sulfate had no effect. Interleukin-2 mixed with TPN solutions showed slightly enhanced growth of the CTLL-2 line compared with the interleukin-2 standard. Mixtures of multiple antibiotics, morphine, and TPN solutions with and without 20% fat emulsion had no effect on interleukin-2 activity. Recombinant interleukin-2 does not lose biological activity when mixed with gentamicin sulfate, tobramycin sulfate, amikacin sulfate, ticarcillin disodium, piperacillin sodium, morphine sulfate, TPN solution, or fat emulsion.