Induction of rat acute-phase proteins by interleukin 6 in vivo.
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 beta-fibrinogen, alpha 2-macroglobulin, cysteine proteinase inhibitor, alpha 1-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 beta-fibrinogen, alpha 2-macroglobulin, cysteine proteinase inhibitor or alpha 1-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 alpha 2-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 alpha 2-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.
Geiger
T
T
Biochemisches Institut, Universität Freiburg, FRG.
Andus
T
T
Klapproth
J
J
Hirano
T
T
Kishimoto
T
T
Heinrich
P C
PC
D000209:Acute-Phase Proteins / Q000096:biosynthesis*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D005786:Gene Expression Regulation / Q000187:drug effects; D015850:Interleukin-6; D007378:Interleukins / Q000494:pharmacology*; D007700:Kinetics; D008099:Liver / Q000187:drug effects; D008297:Male; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D011919:Rats, Inbred Strains; D011994:Recombinant Proteins / Q000494:pharmacology; D014425:Turpentine / Q000494:pharmacology
D000209:Acute-Phase Proteins; D015850:Interleukin-6; D007378:Interleukins; D012333:RNA, Messenger; D011994:Recombinant Proteins; D014425:Turpentine