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The Journal of Nutrition Vol. 128 No. 6 June 1998,
pp. 960-966
Department of Nutrition, Pennsylvania State University, University Park, PA 16802
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ABSTRACT |
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Abstract
Introduction
Methods
Results
Discussion
References
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Plasma retinol is reduced during numerous infections, and inflammation alters the hepatic synthesis of retinol-binding protein (RBP). In this study, we have investigated the effects of endotoxin-induced inflammation on vitamin A (VA) supplementation in a rat model of marginal VA deficiency. Marginally VA-deficient rats received an intraperitoneal dose of lipopolysaccharide (LPS, n = 14) or saline (n = 10); 6 h later, six LPS + VA and six saline + VA rats received 7.1 µmol VA orally. Twenty-four hours after endotoxin administration, rats with inflammation (LPS) had lower plasma retinol, RBP, and hepatic RBP than saline rats (37, 31 and 44%, respectively, P < 0.05). Inflammation did not affect VA concentrations in liver and perirenal adipose tissue, although kidney VA was reduced relative to saline rats. However, urinary VA was not detected. Eighteen hours after VA supplementation, inflammation reduced the plasma unesterified retinol response (P < 0.05) in LPS + VA relative to saline + VA rats, although total VA increased as a result of the presence of retinyl esters in LPS + VA rats. Hepatic esterified retinol concentration was reduced (P < 0.01) in LPS + VA compared with saline + VA rats; however, hepatic unesterified retinol did not differ. Renal total retinol increased in VA-supplemented rats, but urinary retinol excretion, when observed, was low, independently of inflammation. These findings indicate that inflammation-induced hyporetinemia does not necessarily imply a loss of VA, but rather represents a redistribution of tissue VA brought about by a reduced hepatic synthesis of RBP. Practical implications from these collective results are to recommend the determination of both unesterified and esterified retinol to fully assess the plasma response to VA supplementation and to caution the use of VA assessment methodologies that depend on the hepatic synthesis of RBP during acute inflammation.
KEY WORDS: hepatic retinol storage · retinol-binding protein · rats · tissue distribution · urinary retinol excretion
In mammals, plasma vitamin A (VA)6 exists in two forms, as esterified retinol, associated mainly with chylomicra after meals, and as retinol bound to retinol-binding protein (RBP). The concentrations of these forms depend on the prandial and VA status of the subject (Blaner and Olson 1994 In less developed countries in which VA deficiency is a public health problem, VA supplementation of children >12 mo old with a single oral dose of 200,000 IU [60,000 retinol equivalents (RE)] has been advocated as a measure to improve VA status and reduce child mortality (Underwood 1994 Recently, clinical trials conducted in the United States and Chile on the efficacy of VA supplementation to treat respiratory syncytial virus infection (RSV) have shown no reduction of morbidity or mortality (Bresee et al. 1996 Materials.
LPS (Pseudomonas aeruginosa, F-D type 1) was obtained from List Biological, Campbell, CA. Retinol (Aquasol A parenteral, a water-miscible preparation containing 50,000 IU VA/mL as retinyl palmitate), was purchased from Astra, Westborough, MA. Reagent-grade chemicals were obtained from Fisher Scientific, Pittsburgh, PA, or Sigma Chemical, St. Louis, MO.
Animals and experimental design.
Three pathogen-free Sprague-Dawley lactating rats, each with 10 4-d-old female pups were purchased from Charles River Breeding Laboratories (Wilmington, MA). All experimental protocols were in compliance with the NRC Guide for the Care and Use of Laboratory Animals. All animals were housed in plastic cages with wood-chip bedding in a room maintained at 22°C with a 12-h dark:light cycle (with dim yellow light during metabolic experiments). Marginal VA deficiency was induced in rats by feeding purified rodent diet AIN-93M (Reeves et al. 1993 Tissue VA analysis.
Total retinol, unesterified and esterified retinol were determined by HPLC with the use of trimethylmethoxyphenyl-retinol (TMMP-retinol) as an internal standard (Ross 1986 Tissue retinol-binding protein analysis.
The concentration of RBP in plasma and liver was determined in individual samples by a sensitive and specific RIA described previously (Smith et al. 1975 Statistical analysis.
Values are given as the mean ± SEM for individual samples or as the mean and the range for pooled samples. Comparison of means among the four treatment groups (i.e., LPS, saline, LPS + VA and saline + VA) were done with one-way ANOVA, by using the modified least-squared difference post hoc test of significance. The main effects of inflammation and VA supplementation and their interaction were assessed with a two way ANOVA. A two-tailed P-value of
Effect of inflammation on body weight and hydration status.
In Table 1, the changes in body weight, temperature and other variables measured during the 24-h experiment are displayed. Body weight changes did not differ significantly among the groups. All LPS-treated rats responded with an increase in body temperature measured 6 h posttreatment (two-way ANOVA, P < 0.03). Water intake, urine output and hematocrit did not differ among treatment groups, indicating that inflammation did not induce severe plasma volume changes or that the loss of body weight was due to anorexia or food withdrawal.
Inflammation affects the plasma VA response to supplementation.
The plasma VA concentrations of rats without and with inflammation before and after VA supplementation are shown in Figure 1. The pretreatment plasma total retinol concentration of marginally VA-deficient rats averaged 0.78 µmol/L, 60% of that previously determined for VA-sufficient rats [1.3 µmol/L (Rosales et al. 1996b
Inflammation affects the distribution of hepatic VA in marginally VA-deficient rats before and after VA supplementation.
The hepatic concentrations of unesterified retinol (Fig. 2A) and esterified retinol (Fig. 2B) in rats with marginal VA deficiency, without and with inflammation, as well as the hepatic response (unesterified retinol, Fig. 2C, and esterified retinol, Fig. 2D) were measured 24 h after endotoxin or 18 h after VA administration. In saline-treated, marginally VA-deficient rats, the concentration of liver total retinol (the sum of data shown in Fig. 2A + Fig. 2B) averaged 2.2 ± 0.4 nmol/g; of this, ~82% was esterified. Rats with inflammation had the same hepatic total retinol concentration (2.6 ± 0.4 nmol/g liver) as saline rats, but their hepatic unesterified retinol concentration was significantly lower (P < 0.001, Fig. 2A), whereas their hepatic retinyl ester concentration was 36% higher than that of saline rats (Fig. 2B). After a single oral dose of 7.1 µmol of VA, the total retinol concentration (Fig. 2C + Fig. 2D) rose to 223 ± 18 nmol/g liver in rats without inflammation, and to 134 ± 19 nmol/g liver in rats with inflammation (P < 0.01). The rise in unesterified retinol was similar in both VA-supplemented groups, regardless of inflammation (Fig. 2C). However, the increase in esterified retinol was significantly less (P < 0.01) in rats with inflammation (Fig. 2D).
VA in extrahepatic tissues.
Significant quantities of VA recycle between liver and extrahepatic tissues, and are stored in the kidneys and adipose tissue of VA-adequate rats. Therefore, we surveyed extrahepatic VA concentrations in representative pools of kidney and perirenal adipose tissue. Inflammation caused reductions to ~71% of control in renal unesterified retinol in marginally VA-deficient rats (Fig. 3A), and to 52% of control in renal esterified retinol (Fig. 3B). VA supplementation resulted in increased renal unesterified and esterified retinol concentrations. In perirenal adipose tissue, total retinol (Fig. 3C) was not affected by inflammation alone, but was sevenfold greater in VA-supplemented rats without inflammation than in saline rats (saline + VA > saline), and ~fourfold in rats with inflammation than in saline rats (LPS + VA > saline).
VA supplementation, but not inflammation alone, is associated with detectable urinary excretion of retinol.
Retinol was not detected in the urine of any marginally VA-deficient rat without inflammation before VA supplementation (limit of detection 4 ng/dL, or 0.14 nmol/L). It was detected in only one of eight LPS-treated rats before VA supplementation (binomial probability, P = 0.38); this rat's urine contained 1.05 nmol/L of unesterified retinol. After VA supplementation, 50% of rats (3 of 6) without inflammation excreted retinol, whereas 100% of rats (6 of 6) with inflammation excreted VA (both unesterified and esterified retinol; Fisher's exact test, P = 0.18). These analyses show that inflammation per se was not significantly associated with urinary VA excretion. In the absence of VA supplementation, regardless of inflammation, urinary VA excretion was detected in only one of 12 rats, whereas 75% of all VA-supplemented rats (9 of 12) excreted detectable VA in urine ( Inflammation reduces hepatic RBP before and after VA supplementation.
As expected, marginally VA-deficient (saline-treated) rats had hepatic RBP concentrations that were higher, and plasma RBP concentrations that were lower (Table 2) in comparison to those previously reported for VA-sufficient rats (Blaner et al. 1985
In this study we used LPS-induced inflammation in the rat to examine the reduction of plasma retinol during the acute phase of infection. This model reproduces the marked reduction of plasma retinol and its subsequent normalization (Rosales et al. 1996b We thank Nan-qian Li and Amanda Rouen for their assistance with some of the HPLC analyses and handling of experimental animals.
INTRODUCTION
Abstract
Introduction
Methods
Results
Discussion
References
, Blomhoff et al. 1991, Goodman 1984). Under conditions of VA sufficiency, ~60-80% of chylomicron-derived VA is transferred from hepatocytes, the initial site of VA clearance, to stellate cells for storage. In contrast, during VA deficiency, most diet-derived retinol that is cleared by liver is immediately returned to the plasma compartment as retinol bound to RBP (Blomhoff et al. 1991). In VA deficiency, the mRNA for RBP is still transcribed in liver (Soprano et al. 1982), but RBP accumulates because its secretion is dependent on the availability of retinol (Goodman 1984). Thus the provision of retinol to VA-deficient animals or humans induces a rapid increase in the secretion of holo-RBP from liver, resulting in a transient rise in plasma retinol concentration. This change has been used as an indicator of inadequate VA reserves and is the basis of the relative dose response (RDR) and modified relative dose response (MRDR) tests (Loerch et al. 1979, Tanumihardjo et al. 1990).
). Because VA supplementation has been demonstrated to reduce measles morbidity and mortality (Hussey and Klein 1990), WHO and the United Nations International Children's Emergency Fund (UNICEF) have jointly recommended VA supplementation to treat children with measles (WHO/UNICEF 1987). Additionally, the American Academy of Pediatrics has recommended that U.S. physicians follow the WHO guidelines in the treatment of children with measles (Committee on Infectious Diseases 1993).
, Dowell et al. 1996, Quinlan and Hayani 1996). These results are in contrast to those trials showing a reduction of measles morbidity and mortality. Nonetheless, plasma retinol is significantly reduced in children with RSV or with measles virus infection, and this reduction has been shown to be strongly associated with severity of disease (Arrieta et al. 1992, Bresee et al. 1996, Butler et al. 1993, Coutsoudis et al. 1991, Frieden et al. 1992, Hussey and Klein 1990, Markowitz et al. 1989, Neuzil et al. 1994, Quinlan and Hayani 1996). The reduction in plasma retinol is transient, with a return to normal levels [i.e., plasma retinol > 0.7 µmol/L (20 mg/dL)] during convalescence, even in children who have not received VA supplements (Coutsoudis et al. 1991, Neuzil et al. 1994). Taken together, these results have raised questions regarding the meaning of reduced plasma retinol concentration during infection, because it is unclear whether low plasma retinol is indicative of poor VA status (i.e., depletion of VA during infection) or whether such changes occur independently of VA status. If the latter is true, then what are the mechanism(s) involved in mediating the reduction of serum retinol? Because the reduction of plasma retinol during infection is associated with the severity of infection, it is important from a public health perspective to study the mechanism(s) causing this reduction during the acute phase of infection, as well as its consequences on the response to VA supplementation. We showed previously that plasma retinol concentration is reduced by ~50% during the acute inflammatory response to endotoxin (lipopolysaccharide, LPS) in normal, vitamin A-sufficient rats (Rosales et al. 1996b). This reduction paralleled reductions of plasma and liver RBP, which were preceded by a 50% reduction in the abundance of RBP mRNA in liver. The greatest reduction in plasma retinol concentration occurred 24 h after the induction of inflammation, whereas by 72 h, plasma retinol had returned spontaneously toward normal values (Rosales et al. 1996b). The reduced production of RBP, a negative acute phase protein, may result in reduced secretion of retinol-RBP from liver into plasma and, as a consequence, in low plasma retinol-RBP and reduced delivery of retinol-RBP to target tissues, filtration into the kidney and reabsorption back into plasma. This study was designed to determine whether acute inflammation causes severe hyporetinemia during marginal VA deficiency and to assess the effect of inflammation on the response of plasma, liver and peripheral tissues to VA supplementation.
MATERIALS AND METHODS
Abstract
Introduction
Methods
Results
Discussion
References
), modified to contain no VA, to lactating dams and their offspring until the latter were 35-d old. For the next 30 to 40 d, rats were fed the same diet containing 0.3 mg of retinol (as retinyl palmitate)/kg of diet. All rats had free access to water throughout the study; access to food was unlimited until the initiation of the 24-h experiment when food was removed (Rosales et al. 1996b). A blood sample (~0.5 mL) was obtained from a tail vein 1 or 2 d before experimentation to determine base-line plasma retinol concentration.
). Inflammation was induced in 65-d-old rats (n = 14, average body weight 274 g) by a single intraperitoneal injection of 50 µg LPS/100 g body weight dissolved in 1 mL of sterile saline (LPS group); 10 control rats (average body weight 277 g) of the same age and VA status received 1 mL of sterile saline only (saline group). Food was removed immediately and the rats were placed in Nalgene metabolic cages (VWR Scientific, Bridgeport, NJ) until the end of the 24-h experiment.
).
20°C. The liver, kidneys and a sample of perirenal adipose tissue were excised, blotted, immediately frozen in liquid nitrogen and stored at 70°C until they could be processed (Furr et al. 1994). Urine was collected in aluminum foil-wrapped glass tubes containing 0.05 mol/L Tris-HCl, pH 7.5, to avoid formation of precipitates (Mao et al. 1996), and 0.1% thimerosal as an antimicrobial agent. These tubes were removed every 12 h; urine was then centrifuged at 315 × g for 10 min at 20°C and stored under argon at 20°C. Samples were analyzed for unesterified retinol and total retinol within 2 wk of urine collection (Mao et al. 1996).
). Total retinol was extracted with hexanes after saponification of samples, whereas unesterified retinol and retinyl esters were extracted with hexanes from nonsaponified samples. Plasma esterified retinol was calculated as the difference between total and unesterified retinol.
. The validity and reproducibility of retinol determination in urine collected over 12 h were demonstrated by the recovery of essentially all (348 and 372 pmol, 99 and 96%, respectively, n = 2) of the retinol, added as 200 µL of rat plasma to 6 mL of rat urine, after exposure over 12 h to the same ambient conditions under which urine had been collected in metabolic cages.
).
0.05 was considered significant. In the case of hepatic VA concentration, the effect of inflammation on retinol and esterified retinol concentrations was determined by a t test with Bonferroni's adjustment and 
/4 = 0.0125 to assess significance. Exact P-values for binomial distributions were obtained from Table 1 of Rosner (1986), and Fisher's exact test was used when necessary (Rosner 1986).
View this table:
Table 1.
Changes in body weight and other variables measured during inflammation and before and after vitamin A (VA) supplementation of marginally VA-deficient rats1,2
RESULTS
Abstract
Introduction
Methods
Results
Discussion
References
)]. Essentially all plasma retinol was unesterified. Eighteen hours after VA supplementation, plasma total VA increased (two-way ANOVA, P < 0.01). Without inflammation, plasma VA increased by 179% (saline + VA vs. saline), and all of this increase was as unesterified retinol. During inflammation, plasma total VA also increased by 156% (LPS + VA vs. saline). However, the distribution was different; ~33% of the increment was due to the presence of esterified retinol, which was not otherwise detected. Thus inflammation caused a significant reduction in unesterified retinol before VA supplementation and altered the distribution of total retinol between unesterified and esterified retinol after VA supplementation (two-way ANOVA, P < 0.01).
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Fig 1.
Distribution of plasma vitamin A (VA) before and after treatment of marginally VA-deficient rats with lipopolysaccharide (LPS) or supplemental VA. Pretreatment plasma total retinol was determined (see Materials and Methods) in 20 of 24 rats (denoted All). Post-treatment plasma unesterified and esterified retinol were determined in marginally VA-deficient control rats (Saline, n = 4), marginally VA-deficient rats with LPS-induced inflammation (LPS, n = 6), VA-supplemented rats without inflammation (Saline + VA, n = 6) and VA-supplemented rats with inflammation (LPS + VA, n = 6). Inflammation reduced plasma unesterified retinol before supplementation (LPS < saline), and decreased the response to VA supplementation (LPS + VA < saline + VA). Post-treatment plasma esterified retinol, which constituted 33% of plasma total retinol, was found only in the LPS + VA group. Different letters indicate significant differences among treatments (one-way ANOVA, with modified least significance difference test, at P < 0.05).
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Fig 2.
Hepatic unesterified and esterified retinol concentrations in marginally vitamin A (VA)-deficient rats during inflammation, before and after VA supplementation. Unesterified retinol and retinyl esters were determined in liver homogenates from rats treated as indicated in Figure 1. Panel A: There was a significant difference in hepatic retinol (** P < 0.001). Panel B: There was no significant difference in retinyl ester concentration. Panel C: The concentration of hepatic retinol after VA supplementation in rats with inflammation (LPS + VA) did not differ from that of rats without inflammation (VA) (P > 0.05). Panel D: Vitamin A-supplemented rats with inflammation (LPS + VA) had a significantly reduced concentration of retinyl esters compared with rats without inflammation (saline + VA) (* P < 0.01).
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Fig 3.
Renal unesterified retinol and retinyl ester concentrations and total retinol concentrations of perirenal adipose tissue in marginally vitamin A (VA)-deficient rats during inflammation, before and after VA supplementation. Kidneys and perirenal fat samples from rats shown in Figure 1 were pooled into two samples (representing 2-4 rats each) within each treatment group. Data are expressed as the means with the range shown above each bar for the number of pools indicated. Panel A: Kidney unesterified retinol concentration in rats without inflammation (Saline) and with inflammation (LPS), and after VA supplementation in rats without (Saline + VA) and with inflammation (LPS + VA). Panel B: Kidney retinyl ester concentration for the same pooled samples. Panel C: Total retinol concentration in perirenal adipose tissue.
2, P < 0.0001). The median concentration in the latter group was 94 nmol total retinol/L of urine (range 7-499 nmol/L).
, Goodman 1984). A two-way ANOVA showed that inflammation and VA supplementation, independently of each other, significantly affected hepatic and plasma RBP concentrations and plasma RBP saturation (the molar ratio of retinol to RBP) (P < 0.001 for each). Inflammation resulted in lower hepatic RBP and plasma RBP independently of VA supplementation (i.e., LPS < saline, and LPS + VA < saline + VA). However, the response to VA supplementation was not impaired by inflammation, as determined by a lower hepatic RBP and higher plasma RBP 18 h after VA (i.e., the relative response of saline vs. saline + VA rats was similar to that of LPS vs. LPS + VA). As a result of lower concentrations of plasma RBP, plasma RBP saturation was >15% greater in rats with inflammation than in saline-treated rats, independently of VA supplementation (P < 0.001).
View this table:
Table 2.
The effect of inflammation on the concentration of retinol-binding protein (RBP) in liver and plasma of marginally
vitamin A (VA)-deficient rats, before and after VA supplementation1
DISCUSSION
Abstract
Introduction
Methods
Results
Discussion
References
), as observed in clinical studies. Inference from this animal model is justified for the following reasons: first, the administration of endotoxin is a well-established means to induce an acute phase response, similar to that caused by infection (Won et al. 1993); second, the inflammatory response is well conserved among vertebrates (Klasing et al. 1987); and third, the rat has been studied extensively as a model in which to examine the homeostasis of plasma retinol-RBP (i.e., liver secretion, glomerular filtration and tubular reabsorption, Goodman 1984). The results from kinetic studies have corroborated the similarity among rats, monkeys and humans (Blomhoff et al. 1991, Green et al. 1985). Additionally, both normal humans and rats, in contrast to many carnivores, excrete little, if any, VA in urine (Schweigert et al. 1991).
0.7 µmol/L are typically interpreted as an indicator of VA deficiency. Previously we observed a proportionately similar reduction of plasma retinol in VA-sufficient rats [to ~0.8 µmol/L, or 61 ± 4% of pretreatment levels (Rosales et al. 1996b)]. The proportionately similar reductions in plasma retinol in marginally VA-deficient and VA-adequate rats indicate that the effect of inflammation on retinol transport does not depend on VA status.
), may be related to the changes in the distribution of total retinol, unesterified and esterified retinol that were observed for liver and extrahepatic tissues.
, Soprano et al. 1982), RBP is known to accumulate in liver during VA deficiency because retinol is required for the formation of holo-RBP and secretion of this complex into plasma (Muto et al. 1972; Soprano et al. 1981). After VA supplementation, holo-RBP is secreted rapidly from the liver of VA-deficient animals and humans. The response to VA supplementation, estimated by the ratio of RBP concentration in liver after versus before supplementation, may be considered as a proxy for the secretion of holo-RBP. We calculated this ratio of RBP for rats without inflammation and with acute inflammation as follows: 0.10 ± 0.03 (n = 4) for rats without inflammation versus 0.12 ± 0.03 (n = 6) for rats with inflammation (P > 0.05). The similarity between these ratios implies that the livers of marginally VA-deficient rats, whether without or with inflammation, responded to VA supplementation with an output of RBP. Nonetheless, rats with inflammation had much lower absolute concentrations of plasma RBP and retinol than the controls without inflammation. This result implies that, although hepatic holo-RBP could be formed and secreted after VA supplementation in rats with inflammation, the amount of holo-RBP secreted was governed by the availability of RBP in the liver, which was reduced during inflammation. Reductions in hepatic RBP mRNA and protein were demonstrated previously in VA-sufficient rats with endotoxin-induced acute inflammation (Rosales et al. 1996b).
). This suggests that the maintenance of renal retinol-RBP depends on the liver's output of holo-RBP (Smith et al. 1975). In the kidneys of VA-supplemented rats with inflammation, the mean concentration of unesterified retinol was lower than in VA-supplemented rats without inflammation, consistent with an inflammation-induced reduction in hepatic RBP synthesis and, hence, a reduction in plasma retinol-RBP, which leads in turn to a reduction in renal glomerular filtration of VA. In contrast, the concentration of esterified retinol, which is known to be transported by lipoproteins, showed the opposite trend in plasma and kidney. The presence of esterified retinol in plasma 18 h after VA supplementation in LPS-treated rats (Fig. 1) is consistent with an inflammation-induced reduction in the lipolysis and clearance of retinyl ester-containing chylomicra and their remnants (Blaner et al. 1994, Meraihi et al. 1991). Such a reduction could account for the lower concentrations of esterified retinol present in the liver and perirenal fat of LPS + VA-treated rats. However, if chylomicra containing newly absorbed VA enter the glomerular filtrate to be excreted in urine, this may explain the higher concentration of esterified retinol in the kidneys of LPS + VA-treated rats. In carnivores, such a mechanism has been offered as a possible means to eliminate excess dietary VA (Schweigert et al. 1991).
, Stephensen et al. 1994) for retinol determination and demonstrated no loss of retinol added to urine in a 12-h recovery study. Additionally, previous studies on the effect of LPS treatment showed no increase in glomerular filtration rate (Cohen et al. 1990), nor any histopathological changes of renal proximal tubules during inflammation, except in the presence of additional pathology (Ideura et al. 1993). Taken together, these observations provide evidence that inflammation is not necessarily associated with urinary VA excretion, and that hyporetinemia can be explained by a redistribution, rather than by a loss of VA.
, Kjolhede et al. 1995, Rosales et al. 1996a). Our findings in rats would suggest that this lack of increase in plasma retinol may have been due to a reduction of hepatic holo-RBP formation during inflammation. Because inflammation also impairs lipoprotein catabolism, both unesterified and esterified retinol should be determined to fully assess the plasma response to VA supplementation. A practical implication from these collective results is to caution the use of VA assessment methodologies that depend on the hepatic synthesis of RBP because the inflammatory response to infection may, by reducing RBP synthesis, reduce their sensitivity. In this regard, Makdani et al. (1996) have reported that children from the Toledo district of Belize, who are mainly Kekchi and Mayan, had a substantial increase of plasma retinyl ester concentration after they received an oral dose of 450 RE (µg retinol) as part of an RDR test. The authors suggested that either the absorption or the clearance of plasma retinyl ester was delayed in these children and, consequently, fewer children than expected had had positive RDR tests (considered indicative of low hepatic VA stores). This increase in plasma retinyl esters and reduced RDR test parallel our observations in marginally VA-deficient rats with acute inflammation given VA as a supplement. Crooks (1994) has suggested that the poor catch-up growth observed in Mayan children from the Toledo district is an index of their harsh environment (e.g., multiple infectious episodes). Therefore, it is possible that the children studied by Makdani et al. (1996) had subclinical infections at the time the RDR test was conducted. If such were the conditions, inflammation may have reduced chylomicron retinyl ester clearance, as well as the hepatic synthesis of RBP. These changes in retinol metabolism during inflammation could explain both the presence of plasma retinyl esters and the low holo-RBP response observed during the RDR test. The determination of retinol and retinyl esters after VA supplementation may be informative in suggesting whether inflammation has delayed chylomicron metabolism and may also have depressed the synthesis of RBP and, hence, the hepatic secretion of holo-RBP.
ACKNOWLEDGMENTS
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FOOTNOTES |
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Manuscript received 12 November 1997. Initial reviews completed 17 December 1997. Revision accepted 9 February 1998.
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LITERATURE CITED |
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Abstract
Introduction
Methods
Results
Discussion
References
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serum levels and supplementation trial.
Arch. Pediatr. Adolesc. Med.
1996;
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