1. Rats established on a normal (20% protein) diet or a protein-deficient (3% protein) diet were given either a subcutaneous injection of turpentine (5 ml/kg), which induces formation of aseptic abscesses, or saline. Plasma samples were obtained at timed intervals (0–14 days) after the injection for determination of albumin, total protein, α2-macroglobulin (a major acute-phase protein in the rat) and interleukin-6 concentrations. The magnitude and pattern of the acute-phase protein response was then compared with the local inflammatory reaction, assessed histologically, and with changes in the circulating concentration of interleukin-6, which is an important mediator of the acute-phase protein response.
2. After turpentine injection there was an early fall in the plasma albumin and total protein concentrations in both normal and protein-deficient rats. After 12 h the total protein concentration increased in both groups of animals reaching a peak at about 48 h, whereas the plasma albumin concentration continued to fall reaching a minimum at 48 h. The main α2-macroglobulin response was delayed and attenuated in the protein-deficient rats (onset 9 versus 24 h, peak concentration 8.95 ± 0.5 versus 5.33 ± 0.75 g/l, P<0.01, and area under the concentration-time curve 18.43 ± 2.13 versus 7.96 ± 1.48 gl−1 days, P<0.01, in the normal group and protein-deficient group, respectively).
3. The circulating interleukin-6 concentration showed a transient early rise at 1 h, and was followed by a larger more sustained peak at 6–48 h. The onset of the secondary rise preceded the onset of the α2-macroglobulin response in both groups of animals, but both the onset and rate of rise were slower in the protein-deficient animals. The peak concentration of interleukin-6 and the area under the concentration-time curve were not significantly different between the groups. There were also no obvious differences in the intensity of the local inflammatory reaction, although the onset of repair was delayed in the protein-deficient animals.
4. This study confirms that the acute-phase protein response is attenuated by protein deficiency, but this does not appear to be due to an attenuated local inflammatory response after turpentine injection. The delayed onset of the interleukin-6 response may explain the delayed onset of the acute-phase response, but the overall magnitude of the interleukin-6 response (total area under the concentration-time curve), which was similar in the two groups, does not explain the overall attenuation of the α2-macroglobulin response.
Acute-phase response factor, a nuclear factor binding to acute-phase response elements, is rapidly activated by interleukin-6 at the posttranslational level