Induction of rat acute‐phase proteins by interleukin 6 in vivo

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Abstract
Recombinant human interleukin 6 (rhIL 6) was injected i.p. into male Wistar rats to investigate its role as a mediator of the acute‐phase response. Hepatic mRNA levels of β‐fibrinogen, α2‐macroglobulin, cysteine proteinase inhibitor, α1‐acid glycoprotein and albumin were measured at different times after the administration of rhIL 6. Maximal increases of mRNA concentrations were observed already 4 h after the injection of rhIL 6 leading to 4.8‐, 19.7‐, 10‐ and 16‐fold stimulations in mRNA levels of β‐fibrinogen, α2‐macroglobulin, cysteine proteinase inhibitor or α1 acid glycoprotein, respectively. The rhIL 6‐induced stimulation of acute‐phase protein mRNA was much more rapid than the acute‐phase induction after turpentine, where maximal mRNA levels were found between 16 and 24 h. For all acute‐phase proteins studied, the stimulation of mRNA synthesis was found to be dependent on the dose of rhIL 6 injected. In the case of α2‐macroglobulin mRNA a sex‐specific induction by rhIL 6 was found. Only male rats showed an acute‐phase response, whereas in female rats an acute‐phase reaction of α2‐macroglobulin mRNA was not inducible by IL 6. The increases in mRNA levels of the acute‐phase proteins studied were followed by corresponding changes of the proteins in the serum determined by rocket immunoelectrophoresis. It is concluded that IL 6 represents a potent mediator of the acute‐phase response in the rat.