RENAL DISPOSITION OF RECOMBINANT HUMAN INTERLEUKIN-11 IN THE ISOLATED-PERFUSED RAT-KIDNEY

Purpose. To clarify the mechanism of the renal clearance of recombinan t human interleukin-11 (rNL-11), we investigated the renal disposition characteristics of rhIL-11 in the perfused rat kidney. Methods. The d isposition characteristics of In-111-labeled rhIL-11 were analyzed usi ng a single-pass indicator dilution technique and statistical moment a nalysis in the perfused rat kidney under filtering and nonfiltering co nditions. Results. Steady-state distribution volume (V-d) calculated f rom the venous outflow patterns of rhIL-11 at the doses of 0.3 to 10 m u g/kidney was between 0.35 and 0.40 ml/g kidney. However, V-d at the highest dose decreased to a value almost identical to that of bovine s erum albumin, suggesting that there is a reversible and saturable inte raction between the capillary wall and rhIL-11 molecule. In filtering kidney, a remarkable accumulation of rhIL-11 was observed while its ur inary excretion was highly restricted at all doses. In nonfiltering ki dney, rhIL-11 showed a decreased but still significant renal uptake. T aken together, the marked renal uptake of rhIL-11 may be explained by both efficient tubular reabsorption and significant uptake from the ca pillary side. These processes were not saturable within the tested dos e range. These characteristics of rhIL-11 are likely based on non-spec ific electrostatic interaction with the tissues due to its cationic ch arge in the cytokine. Conclusions. The renal disposition processes of rhIL-11 were clarified at organ level in a quantitative manner. These findings agree well with previous observations in an in vivo dispositi on study in mice.