α(2)-macroglobulin and α(1)-inhibitor-3 mRNA expression in the rat liver after slow interleukin-1 stimulation

In this study we have investigated total fiver RNA and the expression of mRNA in the rat fiver in vivo after a slow stimulation of interleukin-1. A total dose of 4 μg interleukin-1β was administered via a subcutaneously implanted osmotic minipump over a period of 7 days. Plasma concentrations of α(2)-macroglobulin manifested a rapid increase, reaching a peak on day 2, while α(1)-inhibitor-3 manifested a marked initial decrease to 50% of the baseline level, followed by a tendency to increase again. For measurement of total RNA and specific mRNAs from the fiver, rats were sacrificed at different times during the experimental period. Total RNA peaked at 6 h, the level being approximately 60% higher than baseline value. Specific mRNA from the liver for α(2)-macroglobulin and α(1)-inhibitor-3 were quantified using laser densitometry on slot blots. The amounts measured during the experimental period agreed with the pattern of corresponding plasma protein levels. From barely detectable amounts at baseline, α(2)-macroglobulin mRNA peaked on day 1, and then declined. Levels of α(1)-inhibitor-3 mRNA manifested an initial increase at 3 h, but then declined and remained low until day 5 when there was a tendency towards an increase. It was concluded that the levels of plasma concentrations of α(2)-macroglobulin and α(1)-inhibitor-3 are mainly regulated at the protein synthesis level, and that long-term interleukin-1β release could not override the initial acute phase protein counteracting mechanism triggered.