Fate of interleukin‐6 in the rat

Abstract

Iodinated recombinant human interleukin-6(¹²⁵I-rhIL-6) was intravenously injected into rats and its fate was studied during 24 h. Between 10–20 min after a single-dose injection, ¹²⁵I-rhIL-6 accumulated in liver as previously reported [Castell et al. (1988) Eur. J. Biochem. 177, 357–361]. After 1 h. the radioactivity disappeared from the liver and accumulated in skin, reaching 35% of injected ¹²⁵I-rhIL-6 5–8 h after injection. No comparable accumulation of radioactivity was found in skin when [¹²⁵I]iodide or rat serum ¹²⁵I-albumin was administered. Finally the radioactivity was detected as [¹²⁵I]iodide in urine. Autoradiograhic analysis of skin sections 5 h after ¹²⁵-I-rhIL-6 injection showed radioactivity in the interstitium. When the experiments were carried out with [³⁵S]rhIL-6, essentially the same results were obtained: a decrease in radioactivity in the liver after 20 min, and a substantial increase in skin 7 h after injection. In vitro experiments showed that ¹²⁵I-rhIL-6 is degraded by rat and human fibroblasts, whereas no degradation was observed with rat hepatoma cells (Fao) or human hepatocytes. These observations suggest the involvement of skin in the catabolism of IL-6.