Effect Of Acute Inflammation Research Articles

Acute inflammation induced by the biopsy of mouse mammary tumors promotes the development of metastasis

Development of metastasis in peripheral tissues is a major problem in the fight to cure breast cancer. Although it is becoming evident that chronic inflammation can contribute to tumor progression and metastasis, the effect of acute inflammation in primary tumor is less known. Using mouse models for breast cancer here we show that biopsy of mammary tumors increases the frequency of lung metastases. This effect is associated with the recruitment of inflammatory cells to the lung and elevated levels of certain cytokines such as IL-6 in the lung airways. Antiinflammatory treatment prior to and after the biopsy reduces the development of metastases triggered by the biopsy. In addition, while lack of IL-6 does not affect primary tumor development, it protects from increasing number of metastases upon biopsy. Thus, our studies show that in addition to chronic inflammation, acute immune response caused by invasive procedures in the primary tumor may cause an increased risk on peripheral metastases, but the risk could be decreased by anti-inflammatory treatments.

In vivo and in vitro anti-inflammatory activity of Harrisonia perforata root extract

Introduction: Harrisonia perforata root is one of the five medicinal plants in Bencha-Loga-Wichien remedy used for the treatment of fever in Thai traditional medicine. This study was aimed to investigate the anti-inflammatory effect and the action mechanism of the ethnolic extract from the root of H. perforata in vivo and in vitro . Methods: Male Wistar rats were divided into 6 groups and treated with either the ethanolic extract of H. perforata at dose 5-400 mg/kg or indomethacin 5 mg/kg or vehicle. Rat paw volume was measured at 1, 2, 3, 4, 5 and 6 h after carrageenan injection. The in vitro mechanism of the antiinfammatory response was investigated through the measurement of mRNA expression of proinflammatory cytokines, TNF-α, IL-6 and IL-1β in the macrophage cell. Lipopolysaccharide-stimulated macrophage, J774A.1 cell, were exposed to different concentration of Harrisonia perforata root extract (12.5-50 μg/ml). mRNA expression, TNF-α, IL-1β and IL-6, were determined by real-time RT-PCR. Results: H. perforata root extract 50-400 mg/kg significantly reduced the effect of acute inflammation in rat paw edema by 28.49%-65.05% at 2 hour after carrageenan injection. Cell viability were not significantly altered by the presence of H. perforata extract 3.125-50 μg/ml. It was found that the maximum inhibitory effect for TNF-α, IL-1β and IL-6 were 49.83, 47.27 and 32.16% respectively. The concentration of the extract produced maximum effect were 50 μg/ml for both TNF-α and IL-1β but for IL-6, it was 12.5 μg/ml. Conclusion: The ethanolic extract from H. perforata root possesses anti-inflammatory effect. This may occur via suppression of proinflammatory cytokines.

Effects of Acute Inflammation Induced in the Rat Paw on the Deep Digital Flexor Tendon

The tendon is commonly affected by inflammation, and in such situations, the tissue undergoes a process of reorganization of the extracellular matrix to improve and regenerate the affected region. Little is known about the mechanisms that trigger inflammation in the tissues surrounding the affected area. The objective of this study was to biochemically and morphologically analyze the deep digital flexor tendon at the peak of acute inflammation in the rat paw. Wistar rats were divided into the following three groups: those that received injection of 1% carrageenan, those that received 0.9% NaCl, and those that received nothing. The deep digital flexor tendon was divided into the distal, proximal, and intermediate regions. For biochemical analysis, the tendons were treated with guanidine hydrochloride and analyzed by sodium dodecyl sulfate-polyacrilamide gel electrophoresis. Proteins, glycosaminoglycans (GAGs), and hydroxyproline were quantified, and metalloproteinases were analyzed. The GAGs were analyzed by agarose gel electrophoresis. Tissue sections were stained with hematoxylin–eosin, toluidine blue, and Ponceau SS. The content of proteins and GAGs was smaller in the group receiving the application of carrageenan. The concentration of hydroxyproline in the two tendon regions that respond to tension forces was higher in the inflammation group. The metalloproteinase-9 was detected in the distal region, and a thicker epitenon with cellular infiltrate was observed in the groups with inflamed paws. Meanwhile, a better organization of collagen bundles was observed in the two tension regions of that same group. Our results show that although the tendon was not directly inflamed, changes in the surrounding structural and biochemical parameters were observed.

The precursor of resolvin D series and aspirin-triggered resolvin D1 display anti-hyperalgesic properties in adjuvant-induced arthritis in rats

Resolution of inflammation is mediated by endogenous molecules with anti-inflammatory and pro-resolving activities and they have generated new possibilities for the treatment of inflammatory diseases. Here, we have investigated the possible anti-hyperalgesic effects of two lipids, aspirin-triggered resolvin D1 (AT-RvD1) and its precursor, 17(R)-hydroxy-4Z,7Z,10Z,13Z,15E,17R,19Z-docosahexaenoic acid (17(R)HDoHE). The anti-hyperalgesic effects of both lipid mediators were evaluated, using mechanical and thermal stimuli, at different time-points in adjuvant-induced arthritis in rats. Cytokine levels were measured, and immunohistochemistry and real-time PCR for pro-inflammatory mediators were also performed. The precursor of resolvin D series, 17(R)HDoHE, given systemically, inhibited the development and the maintenance of mechanical hyperalgesia in acute inflammation. Such effects were likely to be associated with modulation of both NF-κB and COX-2 in dorsal root ganglia and spinal cord. 17(R)HDoHE was also effective against sub-chronic pain. Unexpectedly, repeated treatment with 17(R)HDoHE did not modify paw and joint oedema in the sub-chronic model, while joint stiffness was prevented. Notably, AT-RvD1 exhibited marked anti-hyperalgesic effects in acute inflammation when given systemically. The efficacy of long-term treatment with either 17(R)HDoHE or AT-RvD1 was partly related to decreased production of TNF-α and IL-1β in rat hind paw. Our findings provide fresh evidence for the anti-hyperalgesic properties of 17(R)HDoHE and its pro-resolution metabolite AT-RvD1. Such lipid mediators might be useful for treating pain associated with acute or chronic inflammation. LINKED ARTICLE This article is commented on by Xu and Ji, pp. 274-277 of this issue. To view this commentary visit http://dx.doi.org/10.1111/j.1476-5381.2011.01348.x.

Unilateral nephrectomy causes an abrupt increase in inflammatory mediators and a simultaneous decrease in plasma ADMA: a study in living kidney donors

Asymmetric dimethylarginine (ADMA) is an endogenous inhibitor of nitric oxide synthases (NOS). Reducing inducible NOS activity in acute inflammation seems to be desirable. In vitro data show that ADMA increases in response to inflammatory mediators, yet the effect of acute inflammation in vivo is scarcely studied. The aim of the study was to evaluate ADMA plasma levels before, during, and after the acute (nonbacterial) inflammatory-like state. Plasma ADMA, l-arginine, C-reactive protein, and IL-6 were determined in 24 healthy subjects undergoing living related kidney donation before as well as 1, 6, 12, 24, 72, and 168 h thereafter. Six hours after nephrectomy, ADMA levels decreased compared with baseline (0.488 ± 0.075 vs. 0.560 ± 0.060 μmol/l, P < 0.05). This difference became even more marked 24 h after the operation (0.478 ± 0.083 μmol/l, P < 0.01 vs. baseline), when the proinflammatory cytokine IL-6 peaked. Seven days after unilateral nephrectomy, ADMA levels were elevated above baseline (0.63 ± 0.05 μmol/l, P < 0.001 vs. baseline). l-Arginine levels decreased already 1 h after nephrectomy (97.5 ± 22.5 μmol/l, P < 0.01 vs. baseline) and paralleled the change in ADMA thereafter. At the end of the observation period when inflammation markers were regressing, l-arginine levels were significantly elevated above baseline (160.6 ± 25.1 μmol/l, P < 0.001 vs. baseline). In summary, this is the first study showing that both ADMA and l-arginine decrease temporarily after unilateral nephrectomy coinciding with the increase in inflammatory mediators. The l-arginine/ADMA ratio, a surrogate for NO production capacity, was only altered for <24 h.

Novel insights into the inhibitory effects of Galectin-1 on neutrophil recruitment under flow

Galectin-1 (Gal-1) is a beta-galactoside-binding protein endowed with anti-inflammatory properties. The purpose of this study was to investigate the effects of endogenous and exogenous Gal-1 on neutrophil recruitment onto TNF-treated endothelium. The effect of human recombinant (hr)Gal-1 on markers of neutrophil activation (CD11b expression, P-selectin glycoprotein ligand 1, and L-selectin shedding) was also assessed. Gal-1 inhibited the platelet-activating factor-induced increase in CD11b expression in a concentration-dependent manner, as assessed by flow cytometry. To determine the effects of Gal-1 on neutrophil recruitment, an in vitro flow chamber was used: Preincubation of neutrophils with hrGal-1 significantly decreased the extent of capture, rolling, and adhesion on activated endothelial monolayers. This inhibition was shared with the endogenous protein, as knockdown of endothelial Gal-1 using small interfering RNA resulted in a significant increase in the number of cells captured and rolling. To verify the effects of Gal-1 in an in vivo system, intravital microscopy of Gal-1 null mice and their wild-type counterparts was performed. Leukocyte adhesion and emigration were increased significantly in the cremasteric circulation of Gal-1 null mice inflamed with IL-1beta. These findings indicate that Gal-1 functions to limit neutrophil recruitment onto a TNF-treated endothelium, a property that may underline its inhibitory effects in acute inflammation.

Protective effect of atorvastatin on acute systemic inflammation-induced endothelial dysfunction in hypercholesterolaemic subjects

Recent studies suggest an association between acute inflammation and deterioration of arterial function. The effect of acute inflammation on endothelial function and the role of treatment with statins have not been investigated in subjects with dyslipidaemia. In this randomized, placebo-controlled, double-blind study, we generated a transient systemic inflammation by Salmonella typhi vaccination in 50 volunteers with mild hypercholesterolaemia after 4 days of treatment with atorvastatin 40 mg or placebo once daily. Endothelium-dependent flow-mediated dilation (FMD) of the brachial artery and circulating levels of endothelial and inflammatory markers were measured before and 8 h after the vaccine. Vaccination produced a decline on FMD at 8 h (absolute decrease of 2.55%, P = 0.001), indicating an unfavourable effect on endothelial function. In contrast, in atorvastatin-treated subjects, FMD was preserved after vaccination (decrease of 0.15%, P = 0.005 vs. placebo). The vaccination-induced decline in plasma level of nitric oxide metabolites (by 6.0 micromol/L, P = 0.007) and antioxidant capacity (by 20.6 micromol/L, P = 0.001) in the placebo group were completely abolished by atorvastatin (P = 0.038 and P = 0.005, respectively, vs. placebo). In contrast, atorvastatin had no significant effect on cytokine levels. Acute inflammation is aetiologically associated with the deterioration of vasomotor and systemic endothelial function in hypercholesterolaemic patients. Atorvastatin effectively abrogates these deleterious effects.

Modeling the effect of acute inflammation on gas exchange

12 prediction tasks were considered, consisting of development and recovery from hyperinflammatory states and kidney dysfunction, with predictions ranging from 1 to 4 days in advance. Four different machine learning algorithms were used: decision trees, first-order random forests, Naive Bayes, and tree-augmented Naive Bayes. Results: Criteria for discrimination and calibration were area under the receiver operator characteristic curve of at least 80% and a Hosmer-Lemeshow H-statistic P value greater than .05. Except for the prediction of development of inflammation, all prediction tasks regarding development satisfied the required criteria. Although recovery from kidney dysfunction was predicted up to 4 days in advance, none of the predictions of recovery from hyperinflammatory states satisfied the criteria completely. Table 1 shows results of a subset of prediction tasks. Conclusions: For the ICU database studied and the predictive tasks considered, standard machine learning techniques result in predictive models with good performances according to the selected criteria.

Accumulation of retinol in the liver after prolonged hyporetinolemia in the vitamin A-sufficient rat

We assessed the effects of prolonged reduction of plasma retinol concentrations (hyporetinolemia) on the distribution of tissue vitamin A (VA) and of its active compounds using a model of continuous recombinant human interleukin-6 (rhIL-6) infusion via osmotic minipumps in VA-sufficient male rats. Plasma retinol and retinol-binding protein (RBP) concentrations remained decreased and lower in rhIL-6-treated rats compared with controls from 7.5 h throughout 7 days of infusion (P < 0.001). This reduction was accompanied by a 68% increase in hepatic retinol concentration by 7 days (P < 0.05). Hepatic and renal retinyl palmitate and retinoic acid concentrations did not change, and renal megalin content remained unchanged; hepatic RBP concentrations were 41% lower in rhIL-6-treated rats compared with controls (P < 0.05). These results indicate that instead of being lost, retinol accumulated in the liver during inflammation and that hyporetinolemia was attributable to a decrease in the availability of hepatic RBP. A plausible consequence of the effect of rhIL-6-induced hyporetinolemia is that by 7 days tissues that are dependent on plasma retinol may become deprived of VA. These results have important implications in understanding the mechanism by which measles infection induces hyporetinolemia and VA deficiency of extrahepatic tissues.

Cationic liposome-mediated gene transfer during acute pancreatitis: tissue specificity, duration, and effects of acute inflammation

Production of inflammatory cytokines in the pancreas, lung, and liver is believed to play a major role in the development of severe pancreatitis. This tissue-specific production could lend itself to directed anticytokine gene therapy if an appropriate delivery system could be developed. This study was undertaken to examine a novel approach for the delivery of protein-based therapies to the tissues involved during acute pancreatitis. Healthy mice received an intraperitoneal injection of cationic liposomes and a DNA plasmid containing the chloramphenicol acetyltransferase (CAT) reporter gene. Animals were killed at 12 hours and 1, 2, 3, 7, and 14 days with serum, pancreas, lung, and liver harvested. Acute pancreatitis was induced (cerulein, 50 μg/kg/hr intraperitoneally ×4) in additional mice before or after CAT transfection. The presence of pancreatitis was established in all animals by histologic scoring of pancreata and by serum amylase and lipase levels. CAT transfection efficiency was determined by quantitative CAT enzyme activity within tissue homogenates. Animals that received the liposome were successfully transfected with the CAT gene into the pancreas, lungs, and liver. Maximal transfection in each tissue occurred at 12 hours with decreasing CAT activity over the ensuing 14 days. No healthy animals receiving the CAT gene developed elevations in amylase, lipase, or any histologic parameter of pancreatitis. Transfection efficiency in the pancreas was markedly increased by preexisting or delayed induction of pancreatitis, whereas transfection of the lung and liver was increased to a lesser extent. Gene transfection into the pancreas, liver, and lungs is possible using a cationic liposome delivery system that does not induce pancreatitis or pancreatic inflammation. Pancreatic expression of the gene product is equal to or greater than that of the organs of the reticuloendothelial system and continues at very high efficiency rates during acute pancreatitis.

Effects of acute inflammation on plasma retinol, retinol-binding protein, and its mRNA in the liver and kidneys of vitamin A-sufficient rats

The acute inflammatory response to tissue injury and infection is associated with low concentrations of plasma retinol and its specific transport proteins, retinol-binding protein (RBP) and transthyretin (TTR). To examine the kinetics and mechanism of hyporetinemia, we have induced acute inflammation with lipopolysaccharide (LPS, from Pseudomonas aeruginosa) in rats with adequate stores of vitamin A. Twenty-four h after treatment with LPS (50 micrograms i.p. per 100 g body weight) or saline and food withdrawal, plasma retinol equalled 0.72 +/- 0.06 mumol/L (mean +/- SEM) in five LPS-treated rats versus 1.35 +/- 0.1 mumol/L in five saline-treated rats (P < 0.01). Plasma, liver, and kidney RBP and TTR concentrations were also significantly reduced, but liver and kidney retinol concentrations did not differ between treatment groups. The relative abundance of RBP mRNA in liver (LPS treatment compared to saline treatment) was reduced as early as 12 h (0.44 +/- 0.15, n = 4 pairs, P < 0.02), and continued to be reduced at 24 h (0.57 +/- 0.12, n = 5 pairs, P < 0.02). In the kidney this ratio did not change significantly due to LPS treatment. The relative abundance of cellular retinol-binding protein (CRBP) mRNA in liver and kidney also was not affected by LPS treatment. We infer from these data that inflammation-induced hyporetinemia results from a reduction in the hepatic synthesis of RBP and secretion of the retinol-RBP complex. Moreover, the results imply that plasma retinol concentration is a poor indicator of vitamin A status during inflammation.

Influence of smoking on the expression of various cytokines in murine bronchoalveolar lavage fluid cells

ABSTRACT The cytokine network plays an important role in the pathogenesis of allergic asthmatic lung. As the influence of smoking on cytokine expression should be considered in delineating the cytokine network, the effects of a single exposure and chronic exposure to smoke on the number and cytokine expression of bronchoalveolar lavage fluid (BALF) cells were evaluated. From a total of 126 BALB/c mice, BALF cells were obtained and analyzed using the quantitative reverse transcription-polymerase chain reaction technique (RT-PCR). The bodyweights of chronic smoking mice were found to be lower when compared to those mice that had not been exposed to smoke. The total number of BALF cells increased after smoking without significant differences in cell classification. Spontaneous mRNA expression of interleukin-1α (IL-1α), interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α) and transforming growth factor-β (TGF-1β) was detected in all cases. The time courses of their expression patterns after exposure to smoke were similar between the chronic and single smoking mice, except for TGF-β. The levels of IL-1β, IL-1β and TGF-β mRNA increased immediately after the exposure to smoke in chronic smoking mice, whereas the levels of TGF-β mRNA increased 2 h after exposure in the single smoking mice. Moreover, the increase of IL-1α and TGF-1β mRNA in the early phase after exposure was exaggerated in chronic smoking mice. Thus, repeated exposure to smoke may have caused some alterations in the expression mechanism of cytokines such as TGF-β and IL-1α in BALF cells, while it seemed to cause a repeated pattern of acute inflammation after each exposure. In the evaluation of cytokine expression in BALF cells in smokers with various lung diseases, it is recommended that before taking samples a sufficient time interval after the last exposure to smoke be allowed to avoid the effect of acute inflammation caused by smoking.

Effects of acute and chronic inflammation on the pharmacokinetics of prednisolone in rats.

The effects of acute and chronic stages of carrageenan-induced air-pouch inflammation on the pharmacokinetics of prednisolone were studied in male Wistar rats. Chronic inflammation produced a significant increase in the area under the curve (AUC) of prednisolone compared to control animals (6594 +/- 2144 vs 3530 +/- 2164 micrograms.hr/L). The effect of acute inflammation was not significant (AUC = 4996 +/- 3813). Both acute and chronic inflammation also reduced the in vitro plasma protein binding of prednisolone, the reduction being much greater after chronic inflammation. The AUC of free prednisolone after chronic inflammation was 3141 micrograms.hr/L, compared to 1121 micrograms.hr/L in the control group and 1823 micrograms.hr/L after acute inflammation. The mean values of half-life and apparent volume of distribution at steady-state in each group were similar. These results indicate that prednisolone must be used with caution in the treatment of inflammatory diseases because of higher free concentrations of the steroid.

Distribution of oxytetracycline to tissue cages and granuloma pouches in calves and effect of acute inflammation on distribution to tissue cages

The effect of acute inflammation on oxytetracycline (OTC) distribution was studied in a tissue cage model in calves. An acute inflammatory reaction was induced in tissue cages by injecting lipopolysaccharide (LPS) from Salmonella typhimurium. The distribution of OTC to tissue cage fluid (TCF) was also compared with distribution to fluid from granuloma pouches (GPF). Tissue from LPS-injected cages showed histological changes indicating an acute inflammatory reaction. Concentrations of OTC were higher in LPS cages than in controls; at 1, 2, 4 and 10 h the difference was statistically significant (P less than 0.05). Numerically the overall elimination rate constant (kel) was larger, elimination half-life (t1/2) shorter, peak concentration (Cmax) higher, and time of peak concentration (Tmax) shorter in LPS cages than in controls. The area under the curve (AUC) of OTC was greater and the ratio AUCTCF/AUCserum was higher in LPS cages than in controls. Although statistically significant differences were not found for all the pharmacokinetic parameters, it was concluded that distribution to and elimination from LPS cages were both faster than in controls. Concentration-time profiles of OTC were similar in TCF and GPF in that concentrations were lower and elimination was more prolonged than in serum. Levels were higher in GPF than in TCF up to 3 h after injection; thereafter the relationship was reversed. Distribution to and elimination processes from GPF appeared to be faster than from TCF as numerically kel was higher, t1/2 shorter and Tmax shorter in GPF than in TCF. It was concluded that the granuloma pouch model and the tissue cage model have similarities in distribution and elimination patterns and that differences are most probably due to differences in the ratio of the surface area to the volume.

Stimulation of PG-like substances released into the circulating blood by phospholipase A2 (PLA2) in the rat. Effect of acute inflammation and non-steroidal anti-inflammatory agemts

Stimulation of PG-like substances released into the circulating blood by phospholipase A2 (PLA2) in the rat. Effect of acute inflammation and non-steroidal anti-inflammatory agemts

Effect of acute inflammation on rat apolipoprotein mRNA levels.

Hybridization studies using specific cDNA have been used to determine the mRNA levels for rat apolipoproteins AI, AII, AIV, and E in extracts of rat liver and intestine. The ratios of intestinal mRNA/liver mRNA for apolipoprotein AI (apo AI), apo AIV, and apo E were 1.3, 1.7, and 0.1, respectively. Apo AII mRNA was detected in the liver but not in the intestine. The mRNA levels for apo AII and apo AIV in rat liver decreased during inflammation to minimums of 40% and 25% of normal, respectively. The mRNA levels for apo AIV in the intestine, apo E in the liver and for apo AI in both the liver and intestine did not change significantly during inflammation. The time course for the decrease in the hepatic mRNA levels for apo AIV was similar to those previously observed for the negative acute-phase proteins albumin and transthyretin. The serum levels for apo AIV were not affected by inflammation.

Babesia bovis: the effect of acute inflammation and isoantibody production in the detection of babesial antigens.

Immunoblots of Babesia bovis antigen contain dominant antigens which react not only with antisera to B. bovis but with sera from naive calves recovering from an acute inflammatory reaction. It seems likely these antigens are from the host rather than the parasite.

A new negatively regulated acute-phase phosphoprotein synthesized by rat hepatocytes.

The effect of acute inflammation on the production of the major phosphorylated protein (PP63) excreted by rat hepatocytes was investigated. Both intra- and extracellular forms of the protein labelled with [32P]Pi, [3H]fucose and [35S]methionine were immunoprecipitated with monospecific polyclonal antibodies, and relative rates of PP63 synthesis were measured. The hepatocytes of acutely inflamed rats produced and excreted 85% less 32P- and 3H-labelled PP63 than did control cells. This decreased amount of PP63 did not result from an impairment in the phosphorylation or glycosylation processes or from a blockade in excretion, but rather was found to be due to extensive shut-off in biosynthesis of the protein as measured by [35S]methionine incorporation. Thus PP63 would appear to represent a new negatively regulated acute-phase protein.

Formula omitted] function of canine neutrophils during experimental inflammatory disease

The effect of acute inflammation on neutrophil function in the dog was studied by measuring in vitro phagocytosis and killing of Staphylococcus aureus . Phagocytosis was not impaired after 30 or 60 minutes and bactericidal activity was not impaired after 60 minutes incubation. However, average bactericidal activity after 30 minutes incubation was diminished significantly (P < 0.01). Wide variations in bactericidal activity after 30 minutes incubation during the course of the inflammation did not correlate with neutrophil count, number of toxic neutrophils, or clinical course of the inflammation. These results indicate that a defect in bactericidal activity can occur in dogs with severe inflammatory disease, and that repeated assays, rather than single determinations, may be needed to detect this dysfunction.

The Effect of Acute Inflammation on the Utilization and Distribution of Transferrin-Bound and Erythrocyte Radioiron

Abstract1. In rats with acute turpentine-induced inflammation, there was a reduced reutilization of radioiron from transfused senescent erythrocytes but a normal utilization of transferrin-bound Fe59 after a 40-hour period. There was a pronounced retention of tracer from the nonviable red cells by the livers and spleens of the inflamed animals.2. During inflammation, the plasma iron turnover fell by about 50 per cent, while the fraction of plasma iron removed per hour was increased. However, there was no marked change in the relative distribution of transferrin-bound Fe59 to the liver, spleen and bone marrow (after perfusion). Transferrin-bound Fe59 initially appeared at an increased rate in the circulating red cell mass.3. Following administration of ferric ammonium citrate in order to raise the plasma iron level, there was a rise in the plasma iron turnover of the inflamed rats, in contrast to the control animals. Diversion of radioiron to the liver and spleen was not markedly increased under these conditions.4. It is concluded that the immediate fall in plasma iron turnover and hypoferremia during acute turpentine inflammation results mainly from an inhibition of the release of iron derived from senescent red cells into the plasma. An increased avidity of the liver, and of marrow red cell precursors and/or reticulocytes for plasma iron may accentuate the fall in plasma iron levels. There appeared to be no inhibition of the bone marrow capacity to turn over larger amounts of plasma iron during inflammation. These results may help in the interpretation of disturbances of iron metabolism during the acute inflammatory state.