Renal, volume, and hormonal changes during therapeutic administration of recombinant interleukin-2 in man.
Changes in blood pressure, renal function, and fluid balance were studied in 12 patients receiving intravenous recombinant interleukin-2 (IL-2) (100,000 units/kg every eight hours) over five days for treatment of metastatic melanoma and renal and colorectal cancers. The IL-2 regimen produced progressive hypotension, azotemia, and sodium avidity (fractional excretion of sodium = 0.20 +/- 0.07 percent) despite massive fluid administration (mean: 18.4 liter per five days) and weight gain (mean: 4.0 kg). Plasma renin activity rose. Hypoalbuminemia developed rapidly (3.6 +/- 0.1 g/dl to 2.2 +/- 0.1 g/dl, p less than 0.01) with widespread edema formation despite normal central venous pressures. Hematocrit did not change during the IL-2 period, consistent with a "capillary-leak." Hemodynamic and renal functional changes reversed after the IL-2 regimen was discontinued, but hypoalbuminemia and elevated urinary n-acetyl-glucosaminidase levels persisted after six days. These studies demonstrate widespread hemodynamic and vascular effects of IL-2 administration that limit its safe use and suggest a possible role for the lymphokine in mediating cardiovascular instability under other circumstances, such as endotoxic shock.
D000328:Adult; D001794:Blood Pressure / Q000187:drug effects*; D001835:Body Weight / Q000187:drug effects*; D003110:Colonic Neoplasms / Q000097:blood / Q000188:drug therapy / Q000652:urine; D003404:Creatinine / Q000097:blood*; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D007262:Infusions, Intravenous; D007376:Interleukin-2 / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D007680:Kidney Neoplasms / Q000097:blood / Q000188:drug therapy / Q000652:urine; D008297:Male; D008545:Melanoma / Q000097:blood / Q000188:drug therapy / Q000652:urine; D008875:Middle Aged; D012964:Sodium / Q000652:urine; D014882:Water-Electrolyte Balance / Q000187:drug effects*
D007376:Interleukin-2; D012964:Sodium; D003404:Creatinine