Systemic administration of interleukin-10 is associated with dose-dependent toxicities in Wistar albino rats

Interleukin 10 (IL-10) is a pleiotropic cytokine associated with immunotherapy. PEGylated IL-10 (AM0010) has been suggested as a therapeutic agent and advanced to phase-II clinical trials, which raises concerns about its safety. This study aimed to establish the toxic effects associated with systemic administration of IL-10 in Wistar albino rats.

Rats were randomly divided into four groups receiving a daily intramuscular administration of 0.3mls of normal saline, 500 ng/kg, 1000 ng/kg, and 2000 ng/kg of recombinant murine IL-10 for 21 days. At day 22, rats were euthanized, and blood was collected for hematological, liver, and kidney function analysis. Liver and kidney tissue sections were used for histopathology analysis.

Liver function results showed that levels of total bilirubin (33.63 ± 1.43 µmol/L), direct bilirubin (7.1 ± 0.21 µmol/L), Alanine Aminotransferase (39.18 ± 1.11 U/L), Aspartate Aminotransferase (35.12 ± 0.98 U/L), and Gamma-Glutamyl Transferase (38.9 ± 0.76 U/L) were all significantly higher in the 2000 ng/kg group. For renal function, significantly low values for all parameters were recorded in the high IL-10 dose groups. Increases in red blood cell numbers, monocytes, hemoglobin levels, and hematocrit were IL-10 dose dependent, with the 2000 ng/kg having the highest numbers. Tissue sections from the liver and kidney revealed alterations in organ architecture with increasing IL-10 dose, with the tissue architecture for the 500 ng/kg IL-10 group comparable to that of the negative control group.

Our study demonstrates that a daily IL-10 dose of up to 500 ng/kg has no significant organ function and structure alterations, and above a daily dose of 1000 ng/kg, side effects begin to appear with increasing dose.