Renal Disposition of Recombinant Human Interleukin-11 in the Isolated Perfused Rat Kidney

Abstract

Purpose. To clarify the mechanism of the renal clearance of recombinant human interleukin-11 (rhIL-11), we investigated the renal disposition characteristics of rhIL-11 in the perfused rat kidney.

Methods. The disposition characteristics of ¹¹¹In-labeled rhIL-11 were analyzed using a single-pass indicator dilution technique and statistical moment analysis in the perfused rat kidney under filtering and nonfiltering conditions.

Results. Steady-state distribution volume (V _d ) calculated from the venous outflow patterns of rhIL-11 at the doses of 0.3 to 10 μg/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 serum albumin, suggesting that there is a reversible and saturable interaction between the capillary wall and rhIL-11 molecule. In filtering kidney, a remarkable accumulation of rhIL-11 was observed while its urinary excretion was highly restricted at all doses. In nonfiltering kidney, rhIL-11 showed a decreased but still significant renal uptake. Taken together, the marked renal uptake of rhIL-11 may be explained by both efficient tubular reabsorption and significant uptake from the capillary side. These processes were not saturable within the tested dose range. These characteristics of rhIL-11 are likely based on non-specific electrostatic interaction with the tissues due to its cationic charge 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 disposition study in mice.