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PubMed2002

[Neurogenic inflammation. I. Basic mechanisms, physiology and pharmacology].

Activation of sensory unmyelinated neurons by noxious stimuli evokes the release of neuropeptides, such as substance P and calcitonin gene-related peptide (CGRP) from peripheral nerve endings. These neuropeptides and subsequently released mediators cause a local oedema, hyperaemia and an erythema which extends beyond the site of stimulation (so-called flare response). Since these inflammatory signs depend on the function and integrity of peripheral sensory nervous systems, the response has been termed neurogenic inflammation. Due to the fact that nearly all tissues in mammals including humans are innervated by afferent sensory neurons, this neurogenic inflammation can occur ubiquitously throughout the body. Albeit first evidence showing that sensory neurons contribute to the inflammatory signs, described as antidromic vasodilatation, axon reflex, triple response, neurogenic inflammation, elicited at the level of tissue that they innervate was first obtained more than one hundred years ago, it was in the last two decades that inflammation caused by the release of neuropeptides from afferent nerve endings was recognised as a physiologically and pathologically relevant process. A large number of exogenous and endogenous substances and autacoids may stimulate or sensitise sensory nerve endings, thus simultaneously producing pain and nociceptive responses, as well as neurogenic inflammation. On the basis of recent research a variety of pharmacological substances and antagonists of putative mediators have been identified to modulate or suppress neurogenic inflammation, thus providing a rationale for therapeutical strategies for various diseases in which neurogenic inflammation is suggested to be involved. Among them, capsaicin and other newly developed agonists and antagonists at the vanilloid receptor have attracted particular attention, since they were found to be capable of desensitizing nociceptive nerve structures and thus of preventing development of neurogenic inflammation or even of abolishing an ongoing inflammatory process.

Animals↗
PubMed2006

Factor B of the alternative complement pathway regulates development of airway hyperresponsiveness and inflammation.

Exposure to inhaled allergens leads to increases in airway hyperresponsiveness (AHR) and inflammation, associated with increased levels of biologically active fragments derived from the complement C3 and C5 family of proteins. Further, complement activation during allergen challenge in sensitized animals is necessary for the development of AHR and airway inflammation. To define the complement pathway involved, we studied mice deficient in complement factor 4 (C4-/-), a critical component of the classical pathway, or factor B (fB-/-), an essential protein in the alternative complement pathway. WT, C4-/-, and fB-/- mice were sensitized to ovalbumin and subsequently exposed to nebulized ovalbumin (1% in saline) on 3 consecutive days. After allergen sensitization and challenge, fB-/- mice demonstrated significantly lower airway responsiveness to methacholine and less airway inflammation. In contrast, C4-/- mice showed no reduction in AHR and airway inflammation compared with WT mice. Tissue inflammation, goblet cell hyperplasia, and IL-4, IL-5, and IL-13 levels in BAL fluid were significantly reduced in fB-/- mice compared with C4-/- and WT mice. The development of AHR and airway inflammation in sensitized fB-/- mice could be restored after intranasal administration of purified factor B before the airway challenge. In addition, administration of a neutralizing anti-factor B mAb to sensitized mice before airway challenge reduced the development of AHR and airway inflammation. These results demonstrate that in sensitized hosts complement activation through the alternative pathway after allergen exposure is critical to the development of AHR and airway inflammation.

Animals↗
PubMed2004

Olive oil and its main phenolic micronutrient (oleuropein) prevent inflammation-induced bone loss in the ovariectomised rat.

The present study was designed to evaluate the effect of olive oil and its main polyphenol (oleuropein) in ovariectomised rats with or without inflammation. Rats (6 months old) were ovariectomised or sham-operated as control. Ovariectomised rats were separated into three groups receiving different diets for 3 months: a control diet with 25 g peanut oil and 25 g rapeseed oil/kg (OVX), the control diet with 50 g olive oil/kg or the control diet with 0.15 g oleuropein/kg. The sham-operated group was given the same control diet as OVX. Inflammation was induced 3 weeks before the end of the experiment by subcutaneous injections of talc (magnesium silicate) in one-half of each group. The success of ovariectomy was verified at necropsy by the atrophy of uterine horns. Inflammation, oleuropein or olive oil intakes did not have any uterotrophic activity, as they had had no effect on uterus weight. The plasma concentration of alpha-1-acid glycoprotein (an indicator of inflammation) was increased in OVX rats with inflammation. With regard to bone variables, osteopenia in OVX was exacerbated by inflammation, as shown by a decrease in metaphyseal and total femoral mineral density. Both oleuropein and olive oil prevented this bone loss in OVX rats with inflammation. At necropsy, oleuropein and olive oil consumption had had no effect on plasma osteocalcin concentrations (marker of bone formation) or on urinary deoxypyridinoline excretion (marker of bone resorption). In conclusion, oleuropein and olive-oil feeding can prevent inflammation-induced osteopenia in OVX rats.

Animals↗
PubMed1961

Studies on the pathogenesis of staphylococcal infection. II. The effect of non-specific inflammation.

Studies have been described in which the effect of early and late or established inflammation, upon staphylococcus infection of rabbit skin has been evaluated. Inflammation was produced in skin by thermal, chemical, bacterial and immunological injury, and it was found that the area of inflammation was more susceptible to staphylococcus infection than was normal skin if the bacteria were injected within 2 to 3 days after the injury. When staphylococci were injected into an area of inflammation of over 3 days' duration, there appeared to be an increase in local resistance to infection. The way in which inflammation was produced seemed to have a little influence upon the effects observed. This influence of non-specific inflammation upon staphylococcus infection was compared with the influence of specific bacterial hypersensitivity, which also is associated with an increase in infectivity of the microorganism in sensitized animals. It was concluded that specific bacterial hypersensitivity probably increases susceptibility to infection with the staphylococcus in the same way as non-specific inflammation. The general significance of non-specific inflammation upon infection is also discussed.

Animals↗
PubMed1989

Prevention of lens protein-induced ocular inflammation with cyclooxygenase and lipoxygenase inhibitors.

By the use of fluorophotometry, ocular inflammation induced by lens proteins can be objectively quantified. This method of measuring inflammation was applied to studying the effectiveness of a cyclooxygenase inhibitor, indomethacin, and a lipoxygenase inhibitor, REV 5901, in reducing ocular inflammation induced by lens proteins. Pretreatment with indomethacin prevented the leakage of fluorescein into the anterior chamber up to 2 hrs after intracameral injection of lens proteins. After the first 2 hrs, fluorescein concentration in the pretreated eye rapidly increased to equal the control eye by 4 hrs. When REV 5901 was used to pretreat the eye, there was an increase in fluorescein leakage up to 3 hrs after lens protein injection. However, when a combination of indomethacin and REV 5901 was used to pretreat the eye, there was a significant reduction in fluorescein leakage up to 5 hrs after the injection of lens proteins. The reduction of fluorescein leakage with a combination of indomethacin and REV 5901 was greater than that obtained with prednisolone alone. These results indicate that prostaglandins are the primary mediators of inflammation in the early phase (less than 3 hr) of lens protein induced ocular inflammation and leukotrienes are the primary mediators in the late phase (greater than 3 hr) of lens protein induced ocular inflammation. Also the use of a nonsteroidal antiinflammatory drug which blocks only one arm of the arachidonic acid cascade may potentiate the production of metabolites in the other arm of the cascade. By using a combination of a cyclooxygenase inhibitor and a lipoxygenase inhibitor, metabolites from both arms of arachidonic acid cascade are reduced, hence reducing inflammation in both the early phase and late phase of lens protein induced ocular inflammation.

Animals↗
PubMed2005

Inflammation contributes to low plasma amino acid concentrations in patients with chronic kidney disease.

BACKGROUND: Inflammation and malnutrition are common in chronic kidney disease (CKD) patients, and plasma concentrations of free amino acids (AAs) in these patients are often abnormal. Malnutrition contributes to alterations in AA concentrations. OBJECTIVE: The objective was to study the effects of inflammation on plasma AA concentrations. DESIGN: Concentrations of plasma AAs, serum albumin, and several inflammatory markers were analyzed in 200 fasting, nondiabetic CKD patients who were close to the start of renal replacement therapy. The nutritional status of these patients was assessed by a subjective global assessment. RESULTS: The patients with inflammation [C-reactive protein (CRP) concentrations >10 mg/L] or malnutrition had lower AA concentrations than did the patients with no inflammation or malnutrition. The presence of both inflammation and malnutrition was associated with more marked reductions in AA concentrations than was malnutrition alone. Significant inverse correlations were observed between the plasma concentrations of most of the essential and nonessential AAs and inflammatory markers, whereas serum albumin concentrations were positively correlated with several AA concentrations. A stepwise multivariate regression analysis showed that serum CRP concentrations were independently associated with low concentrations of the sums of both nonessential AAs and all AAs. An analysis of all-cause mortality with a Kaplan-Meier test showed that the patients with higher AA concentrations had significantly better survival than did the patients with lower AA concentrations. CONCLUSIONS: Plasma AA concentrations are low in CKD patients with inflammation and are inversely correlated with concentrations of inflammatory markers. Although inflammation and malnutrition are closely related, CRP concentrations were independently associated with low concentrations of the sums of both nonessential AAs and all AAs, which suggests an independent role of inflammation as a cause of low plasma AA concentrations in CKD patients.

Adult↗
PubMed2004

The effects of serum beta-carotene concentration and burden of inflammation on all-cause mortality risk in high-functioning older persons: MacArthur studies of successful aging.

BACKGROUND: It remains unclear to what extent the associations between low serum beta-carotene concentration and increased risk for cardiovascular disease and cancers are attributable to inflammation. The objective of this study was to evaluate simultaneously the effects of serum beta-carotene concentration and inflammation on the subsequent all-cause mortality risk in high-functioning older persons. METHODS: The authors conducted a prospective cohort study using information from 672 participants from the MacArthur Studies of Successful Aging. Baseline information was obtained for serum concentrations of beta-carotene, C-reactive protein, interleukin-6, cholesterols, and albumin; body mass index; waist:hip ratio; prevalent medical conditions; health behaviors; and medications. Sex-specific univariate and multivariate logistic regression analyses were used to study the effects of low beta-carotene, high inflammation burden, or both on 7-year all-cause mortality rates while adjusting for other confounders. RESULTS: The serum beta-carotene concentration was inversely associated with C-reactive protein and interleukin-6 levels. After adjustment for inflammation markers and other covariates, the relative risks for low beta-carotene for the 7-year all-cause mortality risk were 2.30 (95% confidence interval [CI], 1.23 to 4.31) in men and 0.85 (95% CI, 0.42 to 1.75) in women. Compared with men with high beta-carotene levels and low inflammation, the multiply adjusted relative risk for low beta-carotene and high inflammation burden was 3.78 (95% CI, 1.69 to 8.47) in men. CONCLUSIONS: Low levels of serum beta-carotene are independently associated with an increased all-cause mortality risk in older men, even after adjustment for the effects of inflammation and other risk factors. In men, but not women, a synergistic effect occurs between low beta-carotene concentration and high inflammation burden in predicting higher mortality rates.

Aged↗
PubMed1998

Acute inflammation induces hyporetinemia and modifies the plasma and tissue response to vitamin A supplementation in marginally vitamin A-deficient rats.

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 micromol 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.

Acute Disease↗
PubMed2007

Inflammation, cancer, and targets of ginseng.

Chronic inflammation is associated with a high cancer risk. At the molecular level, free radicals and aldehydes, produced during chronic inflammation, can induce deleterious gene mutation and posttranslational modifications of key cancer-related proteins. Other products of inflammation, including cytokines, growth factors, and transcription factors such as nuclear factor kappaB, control the expression of cancer genes (e.g., suppressor genes and oncogenes) and key inflammatory enzymes such as inducible nitric oxide synthase and cyclooxygenase-2. These enzymes in turn directly influence reactive oxygen species and eicosanoid levels. The procancerous outcome of chronic inflammation is increased DNA damage, increased DNA synthesis, cellular proliferation, disruption of DNA repair pathways and cellular milieu, inhibition of apoptosis, and promotion of angiogenesis and invasion. Chronic inflammation is also associated with immunosuppression, which is a risk factor for cancer. Current treatment strategies for reactive species overload diseases are frequently aimed at treating or preventing the cause of inflammation. Although these strategies have led to some progress in combating reactive species overload diseases and associated cancers, exposure often occurs again after eradication, treatment to eradicate the cause fails, or the treatment has long-term side effects. Therefore, the identification of molecules and pathways involved in chronic inflammation and cancer is critical to the design of agents that may help in preventing the progression of reactive species overload disease and cancer associated with disease progression. Here, we use ginseng as an example of an antiinflammatory molecule that targets many of the key players in the inflammation-to-cancer sequence.

Dietary Supplements↗
PubMed1998

Nitric oxide synthase inhibition and the induction of cytochrome P-450 affect heme oxygenase-1 messenger RNA expression after partial hepatectomy and acute inflammation in rats.

OBJECTIVES: a) To evaluate in vivo, in rat liver, heme oxygenase-1 (HO-1) messenger RNA (mRNA) expression level and the regulation of 3',5'-cyclic guanosine monophosphate (cGMP) production during hepatic regeneration, localized inflammation, and systemic inflammation; and b) to investigate the effect of the induction of cytochrome P-450 and nitric oxide synthase (NOS) inhibition on HO-1 mRNA level and cGMP production in the liver. DESIGN: Experimental, comparative study. SETTING: Biochemical and molecular biology laboratory. SUBJECTS: Six-wk-old male Sprague-Dawley rats (n = 60). INTERVENTIONS: We randomly divided the rats into four groups: a) saline controls; b) animals receiving lipopolysaccharide (600 microg/kg) for systemic inflammation; c) animals receiving turpentine oil (5 mL/kg) for localized inflammation obtained by sterile abscess; and d) partially hepatectomized animals (two-thirds removal of the parenchyma) for hepatic regeneration. MEASUREMENTS AND MAIN RESULTS: Hepatic regeneration induced HO-1 mRNA expression, as shown by quantitative reverse transcription-polymerase chain reaction analysis. The time course of liver HO-1 mRNA induction after partial hepatectomy and localized and systemic inflammation showed a similar and gradual increase, with a maximum at 6 hrs and a return to a minimal level 48 hrs after treatments. Liver HO-1 mRNA was overexpressed during localized vs. systemic inflammation. This overexpression was not correlated with either serum IL-6 or corticosterone concentrations, but is related to increased cGMP production. The administration of phenobarbital, a cytochrome P-450 inducer and of nitro-L-arginine methyl ester, a NOS inhibitor, prevented cGMP production and abolished the overexpression of HO-1 mRNA. CONCLUSIONS: The results of this study indicate that HO-1 mRNA is induced during hepatic regeneration with a similar time course to that observed during acute inflammation. In addition, we demonstrated that: a) HO-1 mRNA is overexpressed during localized vs. systemic inflammation; b) this overexpression is not correlated with IL-6 or corticosterone concentrations but is related to intrahepatic cGMP production; c) induction of cytochromes P-450 and/or inhibition of NOS both reduce liver cGMP production and HO-1 mRNA expression. These results suggest that in rat liver, a cGMP-transducing pathway may control HO-1 mRNA expression. Thus, there may be a role for HO-1 mRNA in the modulation of the hepatic stress response.

Acute Disease↗
PubMed2004

Complete Freunds adjuvant-induced peripheral inflammation evokes glial activation and proinflammatory cytokine expression in the CNS.

Peripheral inflammation induces central sensitization characterized by the development of allodynia and hyperalgesia to mechanical and thermal stimuli. Recent evidence suggests that activation of glial cells and a subsequent increase in proinflammatory cytokines contribute to the development of behavioral hypersensitivity after nerve injury or peripheral inflammation. In the present study, we examined mRNA and protein expression of glial markers and proinflammatory cytokines at the lumbar spinal cord, brainstem and forebrain following intraplantar administration of complete Freunds adjuvant (CFA) in rats. Gene expression studied by real-time reverse transcriptase-polymerase chain reaction (RT-PCR) for microglial markers (Mac-1, TLR4 and CD14) showed a significant increase in their expression during all phases (acute, subacute and chronic) of inflammation. Conversely, up-regulation of astroglial markers [glial fibrillary acidic protein (GFAP) and S100B] was observed only at the subacute and chronic phases of inflammation. Increased immunoreactivity for OX-42 (CR3/CD11b) and GFAP at various brain regions was also observed after the acute and subacute phases of the inflammation, respectively. Quantification of proinflammatory cytokines (IL-1beta, IL-6 and TNF-alpha) at the mRNA (by real-time RT-PCR) and protein level (by ELISA) revealed enhanced expression during the acute, subacute and chronic phases of CFA-induced peripheral inflammation. This study demonstrates that CFA-induced peripheral inflammation induces robust glial activation and proinflammatory cytokines both spinally and supraspinally. In addition, similar to nerve injury-induced behavioral hypersensitivity microglial activation preceded astrocytic activation following CFA-induced peripheral inflammation, supporting a role of microglia in the initiation phase and astrocytes in maintaining hypersensitivity. These findings further support a unifying theory that glial activation and enhanced cytokine expression at the CNS have a role in eliciting behavioral hypersensitivity.

Analysis of Variance↗
PubMed1988

Brain monoamines during carrageenan-induced acute paw inflammation in rats.

Paw inflammation was induced in rats by sub-plantar administration of carrageenan. Significant inflammatory oedema was observed 1 h later and the peak effect was noted between 3-4 h. The oedema was markedly reduced after 12-24 h. Steady state levels of whole brain and hypothalamic monoamines were estimated spectrofluorometrically during the course of the carrageenan-induced paw inflammation. In addition, the rate of accumulation of the brain 5-hydroxytryptamine (5-HT) and noradrenaline (NA) was assessed in clorgyline-pretreated rats during the inflammation. The whole brain and hypothalamic concentrations of 5-HT and NA were augmented during the early phase of the inflammation, but fell below control values when peak inflammation was achieved. Thereafter, the monoamine levels tended to normalize by 24 h when the inflammation had virtually subsided. On the contrary, whole brain and hypothalamic dopamine levels remained largely unaffected. The rate of accumulation of brain 5-HT and NA were enhanced during carrageenan inflammation, indicating that the turnover of these monoamines is augmented during the inflammatory process. The results suggest that acute peripheral inflammation may significantly affect central 5-HT and noradrenergic activity in rats.

Animals↗
PubMed1983

Glycoprotein biosynthesis during the acute-phase response to inflammation.

Inflammation results in an increase in the levels of a variety of glycoproteins in serum. The glycoproteins that respond in this way are usually referred to as acute-phase reactants. Studies on the acute-phase response of rat alpha 1-acid glycoprotein showed that there was an increase in the liver levels of this glycoprotein at 12 h after turpentine inflammation. This was followed by increased serum levels at 48-72 h after inflammation, suggesting a precursor-product relationship between liver and serum alpha 1-acid glycoprotein. Incorporation studies coupled with measurements of synthesis rates of alpha 1-acid glycoprotein showed that increased synthesis was responsible for the acute-phase response of this protein to inflammation. These studies also showed that albumin was a negative acute-phase reactant. The acute-phase response of alpha 1-acid glycoprotein was accompanied by increased liver pools of UDP-N-acetylglucosamine (UDP-GlcNAc) and UDP-N-acetylgalactosamine (UDP-GalNAc) and increased liver activities of glucosamine-6-phosphate synthase and UDP-GlcNAc 2-epimerase. Activities of galactosyl and sialyl transferases in liver were also elevated and serum sialyl transferase was increased substantially in inflammation, suggesting that it may also be an acute-phase reactant. Liver activities of beta-N-acetylhexosaminidase and beta-galactosidase declined by about 50% at 24 h after inflammation; there was evidence that serum levels of these enzymes increased at 24-72 h after inflammation, suggesting that the lysosomal glycosidases may be released from liver during inflammation.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed2004

Bowel inflammation as measured by fecal calprotectin: a link between lifestyle factors and colorectal cancer risk.

The mechanisms by which the lifestyle risk factors obesity, physical inactivity, and low fiber intake predispose to colorectal cancer (CRC) are unclear. Chronic bowel inflammation predisposes to malignancy in cases of inflammatory bowel disease. Many lifestyle risk factors for CRC are associated with evidence of systemic inflammation as indicated by circulating levels of C-reactive protein (CRP), but it is unknown how this relates to inflammation at tissue level. Little is known about the degree of bowel inflammation in general population and the factors that affect it. Therefore, we aimed to assess the relation of levels of bowel inflammation in the general population and lifestyle risk factors for CRC, and to additionally assess whether these associations, if present, were attenuated by controlling for evidence of systemic inflammation. Average CRC risk subjects (320) of either sex aged 50-70 were recruited in South London. A stool sample was provided for calprotectin measurement (a marker of bowel inflammation), serum for CRP, and a detailed dietary and lifestyle questionnaire completed. There was a significant positive relationship between fecal calprotectin and increasing age (P = 0.002), obesity (P = 0.04), physical inactivity (P = 0.01), and an inverse relationship with fiber intake (P = 0.02) and vegetable consumption (P = 0.04). The relationship with obesity was attenuated by controlling for serum CRP. Fecal calprotectin levels are associated with lifestyle risk factors for colorectal cancer. Low-level asymptomatic bowel inflammation may be the link between lifestyle and the pathogenesis of CRC, and circulating proinflammatory cytokines may be part of the mechanism for this link.

Age Factors↗
PubMed2006

Inflammation, a key event in cancer development.

Several recent studies have identified nuclear factor-kappaB as a key modulator in driving inflammation to cancers. Besides this transcription factor, essential in regulating inflammation and cancer development, an inflammatory microenvironment inhabiting various inflammatory cells and a network of signaling molecules are also indispensable for the malignant progression of transformed cells, which is attributed to the mutagenic predisposition of persistent infection-fighting agents at sites of chronic inflammation. As a subverted host response to inflammation-induced tumors, the inflammatory cells and regulators may facilitate angiogenesis and promote the growth, invasion, and metastasis of tumor cells. Thus far, research regarding inflammation-associated cancer development has focused on cytokines and chemokines as well as their downstream targets in linking inflammation and cancer. Moreover, other proteins with extensive roles in inflammation and cancer, such as signal transducers and activators of transcription, Nrf2, and nuclear factor of activated T cells, are also proposed to be promising targets for future studies. The elucidation of their specific effects and interactions will accelerate the development of novel therapeutic interventions against cancer development triggered by inflammation.

Animals↗
PubMed2005

Interleukin-1 gene cluster polymorphisms are associated with nutritional status and inflammation in patients with end-stage renal disease.

BACKGROUND: Wasting and inflammation are two common risk factors for death in patients with end-stage renal disease (ESRD). Interleukin-1beta (IL-1beta) and its receptor antagonist (IL-1Ra) may play a pivotal role in the pathogenesis of wasting and inflammation. METHODS: To investigate effects of the IL-1 gene cluster polymorphisms on wasting and inflammation, we studied 189 ESRD patients (52+/- 12 years, 62% males) close to the start of renal replacement therapy. 205 healthy volunteers served as controls. We analyzed the IL-1B -511C/T, -31C/T, and +3954C/T polymorphisms as well as a variable number of a tandem repeat (VNTR) in IL-1RN. Nutritional parameters included serum albumin level, subjective global nutritional assessment (SGA), and body composition evaluated by dual-energy X-ray absorptiometry (DXA). We used serum high-sensitivity C-reactive protein (hsCRP) as a marker of inflammation. RESULTS: Wasting (SGA>1) was present in 31%, whereas inflammation (CRP>/=10 mg/l) was present in 36% of the patients. The male carriers of the -511T/T and -31C/C genotypes had a lower prevalence of wasting (p<0.05), higher body mass index (BMI) (p<0.05), and higher lean body mass (LBM) (p<0.01). In a stepwise multiple regression model, age (p<0.05), BMI (p<0.01) and the IL-1B -511 genotype (p<0.01) were independently associated with LBM. The carriers of the +3954T allele had a lower prevalence of inflammation (p<0.05) and lower serum hsCRP (p<0.05). The VNTR in IL-1RN was not associated with any markers. CONCLUSION: The investigated IL-1 gene cluster polymorphisms were associated with nutritional status and inflammation in ESRD patients, but marked differences were found between the genders. These polymorphisms could have prognostic utility for predicting wasting and inflammation in ESRD patients.

Adult↗
PubMed2004

Sex differences in severity of inflammation-induced anorexia and weight loss.

Food intake and body weight changes in response to induction of acute inflammation were examined in intact cycling females, ovariectomized females, and sham-operated male rats. In intact females, body weight and feeding responses were compared between rats in which inflammation was induced on day of estrus with rats in which inflammation was induced on day of diestrus. Anorexia and weight loss were more severe in the female rats with inflammation induced on estrus day, which coincides with peak serum estrogen levels. In ovariectomized females, inflammation was induced the day after rats received injections of estrogen, progesterone, or sesame oil (vehicle). Males received vehicle injections. Among female rats, the group that received estradiol injections the previous day displayed the most severe anorexia. The least severe anorexia was observed in female rats that received progesterone the previous day. Food intake of female rats that received vehicle injections prior to induction of inflammation was greater than the rats receiving estrogen but less than the rats receiving progesterone. Male rats displayed the most severe anorexia and greatest weight loss. These data suggest that, although females exposed to estradiol prior to induction of acute inflammation display more severe anorexia than those exposed to progesterone, it may be that progesterone attenuates severity of anorexia rather than estrogen solely potentiating severity. Male rats, however, appear to experience the most severe anorexia in response to this form of inflammation.

Animals↗
PubMed2005

Inflammation causes tissue-specific depletion of vitamin B6.

Previously we observed strong and consistent associations between vitamin B6 status and several indicators of inflammation in patients with rheumatoid arthritis. Clinical indicators, including the disability score, the length of morning stiffness, and the degree of pain, and biochemical markers, including the erythrocyte sedimentation rate and C-reactive protein levels, were found to be inversely correlated with circulating vitamin B6 levels. Such strong associations imply that impaired vitamin B6 status in these patients results from inflammation. In the present study we examined whether inflammation directly alters vitamin B6 tissue contents and its excretion in vivo. A cross-sectional case-controlled human clinical trial was performed in parallel with experiments in an animal model of inflammation. Plasma and erythrocyte and pyridoxal 5'-phosphate concentrations, urinary 4-pyridoxic acid excretion, and the activity coefficient of erythrocyte aspartate aminotransferase were compared between patients and healthy subjects. Adjuvant arthritis was induced in rats for investigating hepatic and muscle contents as well as the urinary excretion of vitamin B6 during acute and chronic inflammation. Patients with rheumatoid arthritis had low plasma pyridoxal 5'-phosphate compared with healthy control subjects, but normal erythrocyte pyridoxal 5'-phosphate and urinary 4-pyridoxic acid excretion. Adjuvant arthritis in rats did not affect 4-pyridoxic acid excretion or muscle storage of pyridoxal 5'-phosphate, but it resulted in significantly lower pyridoxal 5'-phosphate levels in circulation and in liver during inflammation. Inflammation induced a tissue-specific depletion of vitamin B6. The low plasma pyridoxal 5'-phosphate levels seen in inflammation are unlikely to be due to insufficient intake or excessive vitamin B6 excretion. Possible causes of decreased levels of vitamin B6 are discussed.

Adolescent↗