1. The T-cell-derived cytokine interleukin-2 may be used to reverse the immune suppression associated with major surgery. However, both major surgical procedures and recombinant interleukin-2 therapy are known to induce renal dysfunction.
2. Eighteen patients were randomized to receive either recombinant interleukin-2 (18 × 106 i.u./day) or placebo, given subcutaneously for 3 days before undergoing curative colorectal cancer surgery. Indices of renal function were determined pre-operatively and for 21 days after surgery.
3. Pre-operative recombinant interleukin-2 was found to significantly increase, compared with placebo controls, N-acetyl-β-D-glucosaminidase [peak levels 28 (SEM 2) versus 11 (SEM 3) i.u./mmol of Cr] and γ-glutamyltransferase [peak levels 5.3 (SEM 0.6) versus 2.4 (SEM 0.2) i.u./mmol/l] and decrease urinary fractional excretion of sodium [peak difference 0.32 (SEM 0.06) versus 0.76 (SEM 0.08)] (all P < 0.05). Significantly increased urinary excretions of creatinine, N-acetyl-β-D-glucosaminidase and γ-glutamyltransferase were also identified after surgery. All variables returned to pretreatment limits by the seventh day post-operatively, except N-acetyl-β-D-glucosaminidase, which was still significantly elevated 21 days after surgery. No differences in the serum concentrations of sodium, creatinine or urea were observed before or after surgery in either group.
4. Recombinant interleukin-2, when given in the preoperative period, was associated with significant renal dysfunction. However, routine monitoring of serum indices (i.e. sodium, urea, creatinine and albumin) failed to detect such renal damage. These results suggest that, with the use of recombinant interleukin-2 to enhance natural cytotoxicity in the peri-operative period, such therapy may potentiate the renal impairment occurring after surgery.