Reduced response of α 1‐acid glycoprotein (AGP) to recombinanthuman interleukin‐6 (rhIL‐6) in vitamin A‐deficient (VAD) rats

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We examined the association among plasma AGP, C-reactive protein (CRP), retinol, and albumin concentrations using a longitudinal study to estimate a correction function aiding in the interpretation of inflammation-induced hyporetinolemia (HR). VAD (n=4) and sufficient (VAS, n=8) rats received s.c. rhIL-6 (65 μg/kg/d) or PBS (controls) continuously for 3 or 7 d. Plasma samples were collected daily and retinol, AGP, CRP, albumin and total protein were measured. In VAS rats, retinol and albumin decreased (P < 0.05), whereas AGP and CRP increased (P < 0.05), but total protein did not change compared to baseline and controls. In VAD rats, AGP was significantly lower at most time points compared to VAS rats; and, there was an attenuated AGP response to rhIL-6, increasing only to 1/3 of VAS concentrations. A cutoff value indicative of inflammation was calculated for AGP as > 0.108 g/L (95% CI upper limit). Simple linear regression analysis showed an inverse correlation between AGP and retinol (relative to baseline) (y = −0.18x + 0.48, r = −0.84, P < 0.001) for values of AGP > 0.4 g/L. For example, at AGP = 0.4 g/L, retinol decreased to 40% of baseline, and for each 0.1 g/L of AGP increase, retinol decreased an additional 1.8%. This correction function adjusted plasma retinol for inflammation-induced HR in VAS but not in VAD rats. Changes in AGP and albumin were not correlated. In conclusion, for a correction function to work, it is necessary and sufficient that the changes in AGP and retinol have a common underlying mechanism, and that VA status be considered. NIH NIDDK RO3DK062166