Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “INFLAMMATION”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 1,747 records · Page 97Linked to original sources
PubMed2004

Age-related decline in serum parathyroid hormone in maintenance hemodialysis patients is independent of inflammation and dietary nutrient intake.

BACKGROUND: There is a direct relationship between age and serum parathyroid hormone (iPTH) in the normal population, but several studies suggest this relationship is reversed in maintenance hemodialysis (MHD) patients. The pathophysiologic basis of this age-related decline in serum iPTH levels remains unclear, although others have proposed that it is related to low dietary phosphorus intakes. METHODS: We conducted a prospective, cross-sectional evaluation of the relationship between age and serum iPTH levels and factors affecting this relationship. All participating subjects were asked to complete a 3-day food diary. The charts were reviewed to obtain routinely measured laboratory values over the preceding 3 months, and serum was collected to measure markers of systemic inflammation. RESULTS: Ninety-two MHD patients (47 men; age, 51.3+/-14.9 [standard deviation] years; median dialysis vintage, 25.8 months) were studied. Age was inversely correlated with both serum phosphorus and iPTH; these relationships remained significant even when the data were adjusted for diabetic status, dialysis vintage, and dietary nutrient intake. However, there were no associations of age, serum phosphorus, or iPTH with dietary intakes of protein, calories, phosphorus, or calcium either on univariate or multivariate analyses. Markers of systemic inflammation (serum C-reactive protein, and alpha1 acid glycoprotein) did not correlate with age, serum phosphorus, and iPTH or dietary nutrient intake. On the other hand, serum albumin, which may reflect long-term effects of inflammation, did correlate inversely with age and positively with serum phosphorus. CONCLUSIONS: Our cross-sectional study confirms that there are age-related lower levels of both serum phosphorus and iPTH in MHD patients. The mechanisms regarding the inverse relationship between serum phosphorus and age are unclear, but may not be caused by low phosphorus intake or systemic inflammation. In elderly MHD patients, the reduced responsiveness of parathyroid glands may be related to age-dependent accumulation of uremic toxins.

Adult↗
PubMed1999

The variable role of inflammation in acute coronary syndromes and in restenosis.

Inflammation has recently been shown to be an important pathogenetic component of atherosclerosis in general and of acute coronary syndromes in particular. Not only activated inflammatory cells have been found in the plaques, but, more interestingly, also activated circulating inflammatory cells as well as elevated levels of systemic markers of inflammation have been described. Among these, C-reactive protein is of clinical value, as its levels are associated with the outcome. Inflammation is important also in triggering the mechanisms of restenosis and CRP has been recently described as a useful pre-procedure marker of risk of restenosis. The cause of inflammation, what triggers the shift from an indolent disease to the acute coronary syndromes and the more appropriate therapies are still a matter of debate.

Angioplasty, Balloon, Coronary↗
PubMed2001

Results of artificial inflammation in scarless foetal wound healing: an experimental study in foetal lambs.

Recent experimental and clinical evidence suggests that the foetus responds to injury in a fashion fundamentally different from the adult. Foetal wound healing occurs without scar formation. The mechanisms causing this difference are still not well defined but absence of inflammation may play a significant role. The aim of this study was to investigate the effects of artificially induced inflammation on scarless foetal wound healing. Twelve time-dated pregnant ewes underwent hysterotomies at 70 and 90 days' gestation. A potent chemoattractant agent (N-formyl-methionyl-leucyl-phenylalanine) was injected into the upper lip of the foetus in the first operation. In the second operation, a full-thickness incisional wound on the right side and a 3-mm excisional wound on the left side of the upper lip were created and closed primarily. A control wound was created on the lower lip. Macroscopic and histologic examinations of the wounds after birth revealed visible scar lines on the upper-lip wounds but no scar line on the lower lip, and an increase in fibrous tissue and collagen content in the upper-lip wounds. We have shown that injecting a chemotactic agent can stimulate inflammation in a period of gestation when tissue injury can not. Although lack of inflammation due to tissue injury in the early period of foetal life may be an important cause of scarless healing, further experimental studies should be carried out to investigate the pathways that are not activated by tissue injury, the immune status of the foetus and the growth factors involved in the inflammatory response.

Animals↗
PubMed2001

[Effect of duration of phacoemulsification on postoperative inflammation--a retrospective study].

BACKGROUND: The early postoperative inflammation after cataract surgery is mainly caused by surgical trauma. PATIENTS AND METHODS: 450 data-sheets of patients, who were operated for senile cataract with small-incision phacoemulsification and in-the-bag implantation of a foldable intraocular lens were retrospectively analysed. Postoperative inflammation was evaluated with the Laser Flare-Cell Meter Kowa FC-1000 on day 1, 3, 7 and 28. All the operations were done with the same phacomachine model Orbit Oertli. The absolute phacotime was measured, the data classified in steps of 20 seconds. Statistical analysis was made with the student's t-test. RESULTS: In the first postoperative week there is a statistical significant difference in the flare-values between the groups with short phacotime (up to 39 seconds) and the group with long phacotimes (over 80 seconds). One month after operation this significance was absent. CONCLUSIONS: The early postoperative inflammation is influenced by the duration of phacoemulsification. Surgical techniques and phacomachines that may reduce phacotime are helpful with respect to early postoperative inflammation.

Aged↗
PubMed2002

Late effects of TNF-alpha-induced inflammation on the microcirculation of cremaster muscle flaps under intravital microscopy.

In order to understand the microcirculatory changes and regulatory mechanisms governing passage of neutrophils from the vascular bed to the interstitial tissue during ischemia/reperfusion (I/R) injury, a key component of this injury, tumor necrosis factor-alpha (TNF-alpha)-induced inflammation was analyzed. Twenty-four Sprague-Dawley rats were divided into four groups, containing six animals in each. The effect of TNF-alpha-induced inflammation was studied at two different time points, early sequential and late. In the early-effect Groups 1 and 2, animals were given TNF-alpha and vehicle, respectively. Microcirculatory changes were recorded for 6 hr continuously. In the late-effect Groups 3 and 4, following TNF-alpha injection and vehicle, microcirculatory changes were measured 16 hr later. In the early-effect groups, the number of rolling and adhering leukocytes was increased immediately following TNF-alpha injection and remained elevated for the first 3 hr (p<0.05). The number of transmigrated leukocytes remained significantly increased throughout the first 6 hr (p<0.05) and returned to normal at 16 hr. In delayed-effect groups, a second peak in the number of rolling leukocytes was noted at 16 hr (p<0.05). The numbers of rolling and adhering lymphocytes, although remained at the baseline for the first 6 hr, was increased 2- and 1.5-fold at 16 hr, respectively (p<0.05). The number of perfused capillaries gradually decreased over time in the TNF-alpha-induced inflammation groups. A vasodilatory response was noted at the third and fourth order arterioles within the first 3 hr of measurement (p<0.05), but returned to normal afterward. The detrimental effects of TNF-alpha-induced inflammation during I/R injury could be prolonged up to 16 hr at the microcirculatory level of the muscle flaps.

Animals↗
PubMed2006

Heparin-protamine does not aggravate local LPS-provoked leukocytic inflammation in vivo.

OBJECTIVE: Secondary complications involving inflammation limit postoperative results in cardiac surgery. Because heparin-protamine can elicit inflammatory reactions, this study evaluates in vivo whether treatment with heparin-protamine aggravates local endotoxin-induced injury. METHODS: Mice received intravenous injections of either heparin-protamine, protamine alone or PBS for controls, before local air pouch challenge with LPS. Leukocytes recruited within the air pouches were collected and analyzed by flow cytometry. RESULTS: LPS provoked a local leukocytic infiltration in a dose- and time-dependent manner with significantly elevated numbers of 1.75 +/- 0.29 x 10 (6) cells after four hours compared to non-LPS-stimulated controls (0.55 +/- 0.08 x 10 (6) cells). Recruited cells comprised of 74 +/- 4 % PMNLs and 26 +/- 4 % MNLs. The largest fraction of MNLs was positive for the T cell-specific marker CD90.2 (59 +/- 6 %). B cells were only rarely observed (4 +/- 1 %). In non-LPS-challenged air pouches, heparin-protamine provoked a leukocytic infiltration, which was comparable to that observed after LPS (1.51 +/- 0.22 x 10 (6) cells). However, neither heparin-protamine nor protamine alone aggravated the LPS-mediated leukocyte recruitment (2.25 +/- 0.25 x 10 (6) and 1.77 +/- 0.23 x 10 (6) cells). Neither treatment influenced the distribution of leukocyte subpopulations compared to PBS-treated controls. Furthermore, surface expression of CD11a and CD11b on blood leukocytes did not differ between the groups, indicating that protamine does not increase the activation of circulating leukocytes during LPS-induced local inflammation. CONCLUSIONS: Our data indicate that heparin-protamine, although pro-inflammatory in nature, does not aggravate local inflammation provoked by LPS. Thus, enhanced inflammation during the perioperative course of cardiac surgery patients seems not to be attributable to the intraoperative use of heparin-protamine.

Animals↗
PubMed2000

Ligation of IgE receptors causes an anaphylactic response and neutrophil infiltration but does not induce eosinophilic inflammation in mice.

BACKGROUND: Eosinophils are selectively recruited into the tissues during chronic allergic inflammation. IgE is considered an initiator of the allergic reaction; however, the roles of IgE in allergic inflammation are not fully understood. OBJECTIVE: We tested the hypothesis that antigen interaction with specific IgE antibody provokes eosinophilic inflammation. METHODS: BALB/c mice were actively sensitized with ragweed extract and passively sensitized with anti-dinitrophenyl (anti-DNP) mouse IgE and challenged intraperitoneally by injecting either ragweed extract or DNP-ovalbumin (OVA). Immediate anaphylactic responses were examined by monitoring vascular permeability and by measuring histamine content in peritoneal lavage fluids. Late-phase allergic responses were examined by total cell counts and cell differentials. RESULTS: Mice sensitized and challenged with ragweed showed immediate anaphylactic responses followed by temporal increases in neutrophils at 3 to 12 hours and sustained increases in eosinophils in their peritoneal cavities after 24 hours. Double-sensitized mice (ie, sensitized actively for ragweed and passively for DNP-OVA) challenged with ragweed showed immediate anaphylactic responses and peritoneal eosinophilia at 48 hours. Double-sensitized mice challenged with DNP-OVA showed comparable immediate anaphylactic responses but no peritoneal eosinophilia. Furthermore, at 8 hours, ragweed-challenged animals recruited both eosinophils and neutrophils, but DNP-OVA-challenged animals recruited only neutrophils. Finally, after active sensitization and challenge with ragweed, mast cell-deficient mice (WBB6F1-W/W(v)) lacked the immediate response but showed comparable eosinophil accumulation as their litter mate controls (WBB6F1-+/+). CONCLUSION: Interaction of antigen with IgE antibody is insufficient to provoke eosinophilic inflammation in mice.

2,4-Dinitrophenol↗
PubMed2002

Effect of continuing or finishing high-level sports on airway inflammation, bronchial hyperresponsiveness, and asthma: a 5-year prospective follow-up study of 42 highly trained swimmers.

BACKGROUND: Mild eosinophilic airway inflammation and bronchial hyperresponsiveness-ie, mild asthma-have been shown to affect a high proportion of endurance athletes. The persistence of airway inflammation, bronchial hyperresponsiveness, and asthma in this population is not known, however, inasmuch as follow-up studies of athletes' asthma have not been performed. OBJECTIVE: The purpose of this study was to investigate effect of finishing high-level sports on airway inflammation, bronchial hyperresponsiveness, and asthma. METHODS: Forty-two elite competitive swimmers, most of them from the Finnish national team (37/42; 88%), were followed for 5 years in a prospective manner. All of the swimmers completed questionnaires and underwent resting spirometry, histamine challenge testing, and skin prick tests at baseline and at follow-up. Twenty-nine swimmers (69%) also gave induced sputum samples on both occasions. Sixteen (38%) of the swimmers had continued their competitive careers during follow-up (active swimmers), but 26 (62%) had stopped competing more than 3 months before the follow-up examination (past swimmers). RESULTS: Bronchial responsiveness was increased in 7 (44%) of the 16 active swimmers at baseline and in 8 (50%) of the 16 active swimmers at follow-up; it was increased in 8 (31%) of the 26 past swimmers at baseline and in 3 (12%) of the 26 past swimmers at follow-up (McNemar test, P =.025). The difference in the change in bronchial hyperresponsiveness between the study groups was significant (likelihood ratio test, P =.023). Current asthma (defined as bronchial hyperresponsiveness and exercise-induced bronchial symptoms monthly) was observed in 5 (31%) of the active swimmers at baseline and in 7 (44%) of the active swimmers at follow-up; of the past swimmers, it occurred in 6 (23%) at baseline and in 1 (4%) at follow-up (McNemar test, P =.025). The difference in the change in current asthma between the study groups was significant (likelihood ratio test, P =.0040). The sputum differential cell counts of eosinophils and lymphocytes increased significantly during the follow-up period in the active swimmers (Wilcoxon signed rank sum test; P =.033 and P =.0029, respectively); in the past swimmers, the sputum differential cell counts of eosinophils tended to decrease during the follow-up period (P =.17), whereas the differential cell counts of lymphocytes did not change significantly. The changes in the sputum differential cell counts of eosinophils between the study groups differed significantly (Mann-Whitney U test, P =.019). CONCLUSION: In swimmers who had stopped high-level training, bronchial hyperresponsiveness and asthma attenuated or even disappeared. Mild eosinophilic airway inflammation was aggravated among highly trained swimmers who remained active during the 5-year follow-up. Our results suggest that athletes' asthma is partly reversible and that it may develop during and subside after an active sports career.

Adult↗
PubMed2002

Fexofenadine modulates T-cell function, preventing allergen-induced airway inflammation and hyperresponsiveness.

BACKGROUND: Antihistamines have been evaluated for usefulness in the treatment of asthma for more than 50 years. Interest was limited until the introduction of newer compounds that were free of much of the dose-limiting sedation associated with the earlier drugs. OBJECTIVE: In a murine model of allergen-induced airway inflammation and hyperresponsiveness, the efficacy of an H1 receptor antagonist to prevent allergic inflammation and altered airway function was evaluated. METHODS: Mice were sensitized and challenged to an allergen, ovalbumin, which elicited marked airway and tissue eosino-philia and airway hyperresponsiveness. Fexofenadine was administered before challenge, and airway responsiveness to inhaled methacholine, airway and tissue eosinophilia, bronchoalveolar lavage fluid cytokine levels, and serum IgE levels were assayed. In a second group of experiments, sensitized and challenged mice were treated or not treated with fexofenadine before challenge. T cells were isolated from the lungs and adoptively transferred into naive recipients before exposure to limited airway allergen challenge, and lung function and inflammation were evaluated. RESULTS: Fexofenadine treatment of sensitized mice prevented the development of airway hyperresponsiveness in both the primary sensitization and challenge, as well as in the adoptive transfer experiments. These changes were accompanied by decreases in bronchoalveolar lavage and tissue eosinophilia, lymphocyte numbers, and T(H)2 cytokine production. CONCLUSION: The results demonstrate the efficacy of an H1 receptor antagonist in preventing allergen-induced alterations in pulmonary inflammation and airway function. The data support the evaluation of drugs such as fexofenadine in the treatment of allergic asthma.

Adoptive Transfer↗
PubMed2002

Kinetics and mode of peptide delivery via the respiratory mucosa determine the outcome of activation versus TH2 immunity in allergic inflammation of the airways.

BACKGROUND: Specific immunotherapy involving systemic injection of allergen, though highly effective, can cause severe side effects due to IgE-mediated activation of effector cells. Allergen-derived peptides might provide a safer alternative. We have investigated the use of mucosally delivered peptide to induce CD4(+) T(H)2 cell tolerance and thus protect against allergen-induced airway inflammation. OBJECTIVE: The purpose of this study was to investigate whether intranasal administration of an allergen-derived peptide, either alone or adsorbed to chitosan, can prevent the induction of T(H)2-mediated pulmonary inflammation after sensitization and challenge of the airways with allergen. METHODS: Mice were given (intranasally) a peptide containing an immunodominant epitope of the Dermatophagoides pteronyssinus (Der p) 1 allergen, either as soluble antigen or adsorbed to chitosan, before sensitization and allergen challenge. Pulmonary inflammation, antigen-specific CD4(+) T-cell responses, and antibody levels in sera were then determined. RESULTS: Mice given peptide adsorbed to chitosan had significant reductions in airway eosinophilia, which correlated with reduced levels of IL-4 and IL-5 in the bronchoalveolar lavage fluid. There was decreased recruitment of activated CD4(+) T cells into the airways after allergen challenge, which correlated with a loss of Der p 1-specific T-cell cytokine responses in the periphery and the localized production of IL-10 by antigen-specific T cells in bronchial lymph nodes. Induction of peripheral T-cell tolerance was preceded by transient T-cell activation and IFN-gamma production. CONCLUSION: Our data demonstrate that suppression of airway inflammation by intranasal administration of peptide antigen adsorbed to chitosan is initiated by transient T-cell activation and maintained by the production of IL-10 by antigen-specific T cells in the draining lymph nodes.

Administration, Intranasal↗
PubMed2003

Effect of inhaled fluticasone with and without salmeterol on airway inflammation in asthma.

BACKGROUND: The clinical benefit of combining long-acting beta(2)-agonists with inhaled corticosteroids rather than doubling the dose of corticosteroid has been well-documented. However, there are concerns that this might result in a masking of underlying airway inflammation. OBJECTIVE: The aim of this study was to test the hypothesis that the addition of the long-acting beta(2)-agonist salmeterol (SALM) to a low dose of the inhaled corticosteroid fluticasone propionate (FP) has a steroid-sparing effect and does not result in a worsening of bronchial inflammation compared to doubling the dose of inhaled corticosteroid. METHODS: Fifty-six asthmatic subjects, previously not well-controlled on inhaled corticosteroids, were randomized to receive 3 months of treatment with inhaled FP 500 microg twice a day (FP 1000) or FP 200 microg twice a day plus SALM 50 microg twice a day (FP 400 + SALM). Fluticasone propionate 200 microg twice a day served as the control (FP400). Bronchial mucosal biopsy specimens, bronchial washings (BW), and bronchoalveolar lavage were obtained before and after treatment. The primary end points for the study were submucosal mast cell and eosinophil counts. RESULTS: There was a significant improvement in FEV(1) in the FP400 + SALM group compared to both the FP400 and FP1000 groups. This was accompanied by a significant improvement in peak expiratory flow in the FP400 + SALM group in both the morning and evening compared to the FP1000 group. There were no significant between treatment differences in the change in the number of submucosal mast cells or eosinophils. However, in the FP400 + SALM group there was a significant decrease in submucosal mast cells after 12 weeks of treatment. The addition of SALM to FP was not associated with any increases in airway inflammation in the biopsy specimens, bronchoalveolar lavage, or bronchial washings. CONCLUSION: These findings confirm that addition of SALM to FP has clinical benefits but does not mask or exacerbate airway inflammation and suggest that long-acting beta(2)-adrenoceptor agonists might influence mast cell numbers.

Administration, Inhalation↗
PubMed2003

Effects of cysteinyl leukotrienes and leukotriene receptor antagonists on markers of inflammation.

The understanding that asthma pathophysiology includes an inflammatory component has spurred the more aggressive use of anti-inflammatory therapies and created a need for effective tools to measure inflammation. Biomarkers of airway inflammation proposed are obtained by methods that are direct but highly invasive (bronchial biopsy, bronchoalveolar lavage), moderately direct, and less invasive (indirect sputum, exhaled air, breath condensate) or indirect and least invasive (blood, urine). Several studies described in this review have implicated the cysteinyl leukotrienes (CysLTs) as inflammatory mediators in a wide range of diseases, implying that their biological activities reach far beyond acute bronchoconstriction, the activity traditionally ascribed to them. The validity of examining sputum for "biomarkers" has improved the understanding of asthma pathophysiology, optimization of asthma treatment and management, and investigation of the relation between CysLTs and airway inflammation in asthma. Nitric oxide is also a surrogate marker of asthma and reflects airway inflammation. The anti-inflammatory effects of the leukotriene receptor antagonists and the markers of their activity continue to grow.

Anti-Asthmatic Agents↗
PubMedDate not supplied

Use of biological markers of airway inflammation to detect the efficacy of nurse-delivered asthma education.

OBJECTIVE: The purpose of this study was to determine whether analysis of the constituents of induced sputum could be used to document the efficacy of a nurse-delivered patient education intervention and whether changes in the biological markers of inflammation in sputum would correlate with improvements in pulmonary function and symptoms. DESIGN: The study design was prospective, open trial with repeated measures. SETTING: The study took place at a West Coast academic medical center laboratory. SUBJECTS: Subjects included 12 nonsmoking persons with asthma, ages 23 to 51 years, on prescribed daily anti-inflammatory inhaled therapy who had not required oral prednisone in the previous 4 weeks of enrollment. METHOD: The effect of one 30-minute asthma education session on spirometry, peak flow, symptoms, and biological markers of inflammation in sputum was tested for 8 weeks to determine whether biological markers reflect the efficacy of educational interventions. RESULTS: Mean symptom scores decreased and lung function increased slightly over 8 weeks. Markers of eosinophil degranulation decreased by 50% and albumin by 25% from baseline to 8 weeks. Eosinophil percentages dropped 20% over time but did not change consistently at all time points. Clinical markers of asthma control correlated in the low-to-moderate range with biological markers of airway inflammation. CONCLUSION: The results of this study show the effects of a patient education intervention can be detected in both clinical and biological outcomes. Individual education may influence self-care of asthma including adherence to inhaled corticosteroid therapy and thereby suppress airway inflammation.

Adult↗
PubMed2004

E1A and E1B proteins inhibit inflammation induced by adenovirus.

Replication-defective human adenovirus (Ad) group C transducing vectors, most of which have the E1A, E1B, and E3 genes deleted, are highly inflammatory despite the fact that the parental viruses typically cause subclinical or mild infections. To investigate this paradox, the roles that the E1A, E1B, and E3 genes play in inflammation were tested by using replication-incompetent viruses carrying a deletion of the preterminal protein gene. The viruses were injected into BALB/c mouse ears, and edema was monitored as a sensitive surrogate marker of inflammation. A virus deleted for the E1A 289R (transcription activating) protein was noninflammatory, and inhibited edema induced by empty virus particles. The E1A 243R and E1B 55-kDa (p53 binding) proteins play the most important roles in inhibition of inflammation by the noninflammatory virus. The E1B 19-kDa antiapoptotic protein inhibited edema when both the E1A 243R and E1B 55-kDa proteins were expressed but strongly induced edema when only one was expressed. E3 proteins had their greatest effect on the inhibition of edema induced by the E1A 289R protein. The results support a model in which inflammation is countered through a mechanism that involves complex genetic interactions between Ad early region proteins and offer promise for the design and construction of noninflammatory Ad gene therapy vectors that are relatively easy to grow and purify.

Adenoviridae Infections↗
PubMed2005

Role of peripheral corticotropin-releasing factor and urocortin II in intestinal inflammation and motility in terminal ileum.

Corticotropin-releasing factor (CRF) and the closely related family of neuropeptides urocortins (Ucns) are ancient paracrine-signaling peptides secreted in both the central and peripheral neural circuits. CRF and Ucns released from the CNS (central) regulate a plethora of physiological processes that include food intake, inflammation, and bowel motility and permeability. In the gastrointestinal tract, CRF actions are largely proinflammatory, whereas the effects of the Ucn subtypes can be either pro- or antiinflammatory. Central (intracerebroventricular) or peripheral (i.p.) administration of CRF or Ucns inhibits gastric emptying and promotes colonic motility. To ascertain the role of peripherally expressed CRF and UcnII in gastrointestinal inflammation and motility, we generated ileum-specific phenotypic knockouts of these peptides by using RNA interference. Long dsRNA effectively silenced basal expression of CRF and UcnII in ileum. Control dsRNA or saline treatment did not affect CRF or UcnII expression. In an experimental model of toxin-induced intestinal inflammation, inhibition of CRF ablated the inflammatory response (measured by epithelial damage, mucosal edema, and neutrophil infiltration). UcnII dsRNA treatment did not alter the inflammatory response to toxin. Furthermore, ileal motility was increased after site-specific inhibition of both CRF and UcnII. Thus, we demonstrate that ileal-specific CRF promotes inflammation and both CRF and UcnII modulate bowel motility.

Analysis of Variance↗
PubMed2005

Intestinal inflammation-induced growth retardation acts through IL-6 in rats and depends on the -174 IL-6 G/C polymorphism in children.

Inflammatory diseases frequently impair linear growth. Crohn's disease inhibits growth in up to one third of affected children. In rats with trinitrobenzenesulphonic acid-induced colitis, 40% of growth impairment is attributable to inflammation, with the rest being due to undernutrition. In transgenic mice without inflammation, raised IL-6 retards growth, suppressing insulin-like growth factor (IGF)-I. We hypothesized that IL-6, induced by intestinal inflammation, suppresses growth and inhibits IGF-I expression. Therefore, an anti-IL-6 Ab was given to rats with trinitrobenzene-sulphonic acid colitis. The Ab did not improve nutrient intake or decrease inflammation compared with untreated disease controls, but it significantly restored linear growth (P = 0.023) and increased IGF-I (P = 0.05). In humans, the IL-6 -174 G/C promoter polymorphism affects IL-6 transcription, with the GG genotype inducing the greatest IL-6 levels. Because IL-6 is increased in Crohn's disease, we further hypothesized that growth failure would vary with the IL-6 -174 genotype. At diagnosis, among 153 children with Crohn's disease, those with the IL-6 GG genotype were more growth-retarded than those with the GC or CC genotypes (height SD score, -0.51 vs. -0.10; P = 0.031). Also, the patients with the IL-6 GG genotype had higher circulating levels of C-reactive protein, an IL-6-induced product (36 vs. 18 mg/dl, P = 0.028). However, their risk of developing Crohn's disease was similar to other genotypes when compared with 351 healthy controls (P = 0.7). Thus, the IL-6 -174 genotype mediates growth failure in children with Crohn's disease.

Animals↗
PubMed2003

Intracellular localization of differentially regulated RNA-specific adenosine deaminase isoforms in inflammation.

Adenosine-to-inosine (A-to-I) RNA editing is a post-transcriptional process that amplifies the repertoire of protein production. Recently, the induction of this process through up-regulation of the editing enzyme RNA-specific adenosine deaminase 1 (ADAR1) was documented during acute inflammation. Here we report that the inflammation-induced up-regulation of ADAR1 involves differential production and intracellular localization of several isoforms with distinct RNA-binding domains and localization signals. These include the full-length ADAR1 (p150) and two functionally active short isoforms (p80 and p110). ADAR1 p80 starts at a methionine 519 (M519) due to alternative splicing in exon 2, which deletes the putative nuclear localization signal, the Z-DNA binding domain, and the entire RNA binding domain I. ADAR1 p110 is the mouse homologue of the human ADAR1 110-kDa variant (M246), which retains the second half of the Z-DNA binding domain, all RNA binding domains, and the deaminase domain. Additional variations are found in the third RNA binding domain of ADAR1; they are differentially regulated during inflammation, generating isoforms with different levels of activities. Studies in several cell types transfected with ADAR1-EGFP chimeras demonstrated that the p150 and p80 variants are localized in the cytoplasm and nucleolus, respectively. In agreement with this observation, endogenous ADAR1 was identified in the cytoplasm and nucleolus of mouse splenocytes and HeLa cells. Since the ADAR1 variants are differentially regulated during acute inflammation, it suggests that the localization of these variants and of A-to-I RNA editing in the cytoplasm, nucleus, and nucleolus is intracellularly reorganized in response to inflammatory stimulation.

Adenosine↗
PubMed2003

Spontaneous rupture of the Achilles tendon is preceded by widespread and bilateral tendon damage and ipsilateral inflammation: a clinical and histopathologic study of 60 patients.

60 consecutive patients with spontaneous rupture of the Achilles tendon (AT) underwent surgery. Biopsies were taken at the operations from the site of the rupture, the proximal part, the calcaneal insertion, and the peritendium of the injured tendon. A percutaneous needle biopsy was taken from the contralateral (uninjured) AT. On histological examination, collagen degeneration, tenocyte necrosis, and acute inflammation were found at the rupture site in all cases. In the proximal part and at the insertion, degeneration was present in 56/56 and 51/55 of the cases, necrosis in 55/56 and 50/55, and acute inflammation in 49/56 and 35/55, respectively. The severity of the histological changes decreased from the rupture site to the proximal part to the site of insertion, and showed no relation to the age of the patients or the time from the rupture to the operation. Peritendineal vascular changes were minor. In the contralateral AT, degeneration and necrosis were present in 47/50 and 42/50 of the cases, respectively, but the severity of the changes was less than in the injured tendon. Acute inflammation was present in only 1 case. Spontaneous rupture of AT seems to be preceded by widespread, bilateral damage of the tendon and widespread ipsilateral acute inflammation.

Achilles Tendon↗