Pharmacokinetic and biodistribution profile of recombinant human interleukin-10 following intravenous administration in rats with extensive liver fibrosis

Pharm Res. 2004 Nov;21(11):2072-8. doi: 10.1023/b:pham.0000048199.94510.b0.


Purpose: Because interleukin-10 (IL-10) seems a promising new antifibrotic drug, we investigated the pharmacokinetic and biodistribution profile of this potent therapeutic cytokine in rats with extensive liver fibrosis (BDL-3). IL-10 receptor expression was also determined in relation to these aspects.

Methods: To study the pharmacokinetic and biodistribution of IL-10, rhIL-10 was labeled with 125-iodine. Plasma samples of 125IrhIL-10 were obtained over a 30-min time period after administration of radiolabeled-cytokine to BDL-3 and normal rats. The tissue distribution was assessed 10 and 30 min after i.v. administration of 125IrhlL-10. IL-10 receptor expression was determined by immurohistochemical staining and RT-PCR technique.

Results: . The 125IrhIL-10 plasma curves followed two-compartment kinetics with a lower AUC in BDL-3 rats as compared to control. Plasma clearance and distribution volume at steady state were larger in BDL-3 rats. Tissue distribution analysis in normal rats showed that 125IrhIL-10 highly accumulated in kidneys. In BDL-3 rats, the liver content of 125IrhIL-10 increased by a factor of 2, whereas kidney accumulation did not significantly change. Immunohistochemical staining and RT-PCR analysis showed that IL-10 receptor was clearly upregulated in BDL-3 rat livers.

Conclusions: . In normal rats, 125IrhIL-10 rapidly disappears from the circulation, and the kidney is predominantly responsible for this. In BDL-3 rats, the liver largely contributes to this rapid plasma disappearance, probably due to an increase in IL-10 receptor expression. The extensive renal clearance of IL-10 in vivo may limit a clinical application of this cytokine for the treatment of chronic liver diseases. To optimize the therapeutic effects of IL-10 in hepatic diseases, alternative approaches that either decrease renal disposition or that further enhance hepatic delivery should be considered.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Area Under Curve
  • Dose-Response Relationship, Drug
  • Humans
  • Injections, Intravenous
  • Interleukin-10 / metabolism
  • Interleukin-10 / pharmacokinetics*
  • Iodine Radioisotopes
  • Isotope Labeling
  • Liver Cirrhosis / metabolism*
  • RNA, Messenger / biosynthesis
  • RNA, Messenger / genetics
  • Rats
  • Receptors, Interleukin / biosynthesis
  • Receptors, Interleukin / metabolism
  • Recombinant Proteins / pharmacokinetics
  • Reverse Transcriptase Polymerase Chain Reaction
  • Tissue Distribution


  • Iodine Radioisotopes
  • RNA, Messenger
  • Receptors, Interleukin
  • Recombinant Proteins
  • Interleukin-10