Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “INFLAMMATORY MECHANISMS”

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 127 records · Page 7Linked to original sources
PubMed1999

T cell-mediated and non-specific inflammatory mechanisms contribute to the skin pathology of HPV 16 E6E7 transgenic mice.

One of three lines of mice transgenic for the E6 and E7 genes of human papillomavirus type 16 (HPV16) expressed from an alphaA-crystallin promoter also expresses the transgene ectopically in the skin. This line, designated alphaACE6E7#19, develops skin disease from 3 months of age, characterised by epidermal hyperplasia and eventual skin loss. Administration of complete Freund's adjuvant (CFA) to alphaACE6E7#19 mice, but not to non-transgenic littermate controls, induced local epidermal hyperplasia which was histologically similar to the spontaneously arising skin pathology. Local application of 2,4-dinitrochlorobenzene (DNCB) to DNCB-sensitised alphaACE6E7#19 mice, but not DNCB-sensitised controls, also induced hyperplasia. Treatment with cyclosporin A (CsA) or systemic depletion of CD4+ cells significantly reduced the incidence of skin disease. These data suggest that local inflammation, and cytokines produced by T helper cells, contribute to the induction of hyperplastic skin disease in alphaACE6E7#19 mice. Spontaneous skin disease with similar histological appearance, frequency, age of onset and severity in alphaACE6E7#19 mice was observed in scid-/- alphaACE6E7#19 mice, despite immune paresis. Antigen-specific immune responses and T-cell cytokines are therefore not necessary for the induction of skin disease. We propose that epidermal hyperplasia associated with HPV16 E6 and E7 expression in skin is accelerated by local secretion of pro-inflammatory cytokines, whose production can be enhanced by activated CD4+ T cells.

Age Factors↗
PubMed2001

C-reactive protein elevation in patients with atrial arrhythmias: inflammatory mechanisms and persistence of atrial fibrillation.

BACKGROUND: Atrial fibrillation (AF) may persist due to structural changes in the atria that are promoted by inflammation. C-reactive protein (CRP), a marker of systemic inflammation, predicts cardiovascular events and stroke, a common sequela of AF. We hypothesized that CRP is elevated in patients with atrial arrhythmias. METHODS AND RESULTS: Using a case-control study design, CRP in 131 patients with atrial arrhythmias was compared with CRP in 71 control patients. Among arrhythmia patients, 6 had frequent atrial ectopy or tachycardia, 86 had paroxysmal AF, 39 had persistent AF lasting >30 days, and 70 had lone arrhythmias. CRP was higher in arrhythmia than in control patients (median, 0.21 versus 0.096 mg/dL; P<0.001). Arrhythmia patients in AF within 24 hours before sampling had higher CRP than those in sinus rhythm (0.30 versus 0.15 mg/dL; P<0.001). CRP in controls was not different than in patients with atrial ectopy or tachycardia. Lone arrhythmia patients had a CRP of 0.21 mg/dL, which was not significantly lower than arrhythmia patients with structural heart disease (CRP, 0.23 mg/dL) but higher than controls (P=0.002). Persistent AF patients had a higher CRP (0.34 mg/dL) than paroxysmal AF patients (0.18 mg/dL; P=0.008); both groups had higher CRP levels than controls (P</=0.005). CONCLUSIONS: CRP is elevated in AF patients. This study is the first to document elevated CRP in non-postoperative arrhythmia patients. These findings are reinforced by stepwise CRP elevation with higher AF burden. Although the cause of elevated CRP levels in AF patients remains unknown, elevated CRP may reflect an inflammatory state that promotes the persistence of AF.

Analysis of Variance↗
PubMed1992

Inflammatory mechanisms in the passive cutaneous anaphylactic reaction in the rabbit: evidence that novel mediators are involved.

1. We have examined the mechanisms of local oedema formation in the passive cutaneous anaphylactic (PCA) reaction in the rabbit. 2. IgE-containing antiserum was injected i.d. and allowed to sensitize skin sites for periods up to 240 h. Antigen (bovine gamma globulin) was injected i.d. or i.v. and local oedema formation assessed by the accumulation of i.v. injected 125I-labelled rabbit serum albumin. Potential inhibitors were mixed with antigen prior to i.d. injection or were administered i.v. 3. Maximum oedema formation was observed when a sensitization period of 48-72 h was used. Oedema formation in the PCA reaction was of short duration with a t 1/2 of approximately 15 min. No evidence of late oedema formation (up to 6 h) was found. 4. Local oedema formation in the PCA was reduced by indomethacin suggesting that vasodilator, oedema-potentiating prostaglandins were released. However, it was likely that other vasodilators were also generated. 5. Antihistamines were poor inhibitors of oedema formation as were PAF antagonists, a 5-lipoxygenase inhibitor, a kallikrein inhibitor, a bradykinin antagonist and anti-C5a antibody. 6. Local oedema formation in the PCA was partially reduced by neutrophil depletion and colchicine suggesting that neutrophil-dependent mediators were involved. 7. Exudate fluid from anaphylactic reactions in the rabbit peritoneal cavity contained permeability-increasing activity when injected into rabbit skin. This activity is now being characterized. 8. A vasodilator prostaglandin appears to be released in the rabbit PCA reaction but none of the established permeability-increasing mediators appears to be involved. Thus, there may be novel inflammatory mediators generated in this reaction which may have relevance for human allergic skin diseases.

Animals↗
PubMed2006

Spironolactone prevents diabetic nephropathy through an anti-inflammatory mechanism in type 2 diabetic rats.

Aldosterone induces myocardial fibrosis and vascular inflammation via proinflammatory and profibrotic cytokines. The effect of spironolactone on renal inflammation and renal function was investigated in type 2 diabetic rats. For define the molecular mechanism of spironolactone, the effect of spironolactone on the synthesis of monocyte chemotactic peptide-1 (MCP-1) and its upstream transcription factor, NF-kappaB, was evaluated in cultured mesangial cells and proximal tubular cells. There were no changes in blood glucose concentration or BP after spironolactone treatment. Spironolactone treatment significantly reduced urinary albumin excretion and ameliorated glomerulosclerosis. Urinary levels of MCP-1 were significantly increased concurrently with renal expression of MCP-1, macrophage migration inhibitory factor, and macrophage infiltration. Spironolactone treatment significantly inhibited urinary excretion of MCP-1 as well as renal MCP-1 and migration inhibitory factor expression and macrophage infiltration. In addition, aldosterone induced upregulation of MCP-1 expression and NF-kappaB transcriptional activity in cultured cells, and spironolactone reduced both NF-kappaB activation and MCP-1 synthesis. Furthermore, NF-kappaB inhibition abolished aldosterone-induced MCP-1 production. Overall, these findings suggest that aldosterone-induced NF-kappaB activation leads to activation of proinflammatory cytokines, ultimately leading to renal injury in this model. These data suggest that mineralocorticoid blockade may be a potential therapeutic target in diabetic nephropathy.

Animals↗
PubMed2000

Immune-inflammatory mechanisms in IFNgamma-mediated anti-tumor activity.

IFNgamma is a functionally pleiotropic cytokine which shows considerable potency in promoting anti-tumor functions in vivo. Despite limited efficacy when delivered systemically either to experimental animals or patients, IFNgamma appears to play an important and perhaps critical role in directing the development of immune-mediated tumor destruction when expressed within the tumor bed. This has been demonstrated both by use of tumor cells transduced to express IFNgamma and by the use of IL-12 which is able, at least is murine models, to promote an IFNgamma-dependent, T cell mediated anti-tumor response. Recent studies indicate that the therapeutic efficacy of IFNgamma in tumor models depends critically upon the ability of the tumor cells themselves to respond to IFNgamma. Though IFNgamma is able to induce anti-viral activity and has direct anti-proliferative effects on some tumor cell lines, immunomodulatory function also appears to be an important component of its anti-tumor action. This is mediated through the action of several different classes of IFNgamma-inducible gene expression which control antigen processing and presentation, leukocyte trafficking, and indirect tumor cytotoxicity.

Animals↗
PubMed1998

Management of cutaneous lupus erythematosus with low-dose methotrexate: indication for modulation of inflammatory mechanisms.

There is no consensus about an effective and safe treatment for patients with cutaneous lupus erythematosus (LE) who are refractory to antimalarials and/or low-dose oral glucocorticosteroids. Therefore, we retrospectively analyzed the clinical data and laboratory findings of 12 patients who received weekly administrations of 10-25 mg methotrexate (MTX). Previous treatment with antimalarials and/or glucocorticosteroids was not effective or had to be withdrawn because of side effects. Of 12 patients, ten showed improvement of their skin lesions; two patients did not respond to low-dose MTX; two patients cleared rapidly, and five other patients had long-lasting remissions of 5-24 months after stopping MTX treatment. A reduction of circulating autoantibodies was detected in five patients. In all patients, MTX was well tolerated subjectively and objectively. Weekly low-dose MTX is useful for the treatment of cutaneous LE, particularly in those cases which need long-term treatment and/or do not respond to standard therapeutic regimens.

Administration, Oral↗
PubMed2002

Inflammatory mechanisms in cervicogenic headache: an integrative view.

Cervicogenic headache is a relatively common and still controversial form of headache that originates from the neck structures. The pathophysiology probably results from various local pain-producing factors, such as intervertebral dysfunction, but the frequent coexistence of a history of head traumas still plays an important role. This report represents a series of pathophysiologic studies performed for patients with cervicogenic headache and the results achieved by a new pharmacologic treatment for the disease.

Cervical Vertebrae↗
PubMed2005

Inflammatory mechanisms underlying the rat pulmonary neutrophil influx induced by airway exposure to staphylococcal enterotoxin type A.

Association between staphylococcal infection and pathogenesis of upper airways disease has been reported. This study aimed to investigate the mechanisms underlying the rat pulmonary inflammation induced by airway exposure to staphylococcal enterotoxin A (SEA). SEA (0.3-10 ng trachea(-1)) caused dose-dependent neutrophil accumulation in BAL fluid, reaching maximal responses at 4 h (25-fold increase for 3 ng trachea(-1)). Significant accumulation of both lymphocytes and macrophages in BAL fluid was also observed at 4 h (2.1- and 1.9-fold increase, respectively, for 3 ng trachea(-1)). At later times (16 h), neutrophil counts in bone marrow (immature forms) and peripheral blood increased by 63 and 81%, respectively. SEA failed to directly induce chemotaxis and adhesion of isolated neutrophils. Analysis of mRNA expression for iNOS, COX-2 and CINC-2 in lung tissue showed an upregulation of these enzymes, which paralleled elevated levels of LTB4, PGE2, TNF-alpha, IL-6 and NO2- in BAL fluid. Expression of CINC-1 was unchanged, whereas CINC-3 was reduced in SEA-treated rats. Incubation of isolated alveolar macrophages with SEA (3 microg ml(-1)) resulted in significant elevations of TNF-alpha and NO2- levels in the cell supernatants. Dexamethasone (0.5 mg kg(-1)), celecoxib (3 mg kg(-1)) and compound 1400 W (5 mg kg(-1)) markedly reduced SEA-induced lung neutrophil influx and NO2- levels in BAL fluid. The lipoxygenase inhibitor AA-861 (100 microg kg(-1)) partly inhibited the neutrophil influx in SEA-treated rats without modifying the NO2- levels. None of these treatments reduced the number of mononuclear cells in BAL fluid (except of dexamethasone, which abolished the increased lymphocyte counts). Our study shows that airways exposure to SEA results in marked neutrophil influx through mechanisms involving increased expressions of CINC-2, iNOS and COX-2, as well as enhanced production of NO, PGE2, LTB4, TNF-alpha and IL-6.

Animals↗
PubMed1998

Inflammatory mechanisms in childhood asthma.

There is now a reasonable body of data that would suggest that the immunopathology of asthma is similar, if not identical, in childhood asthmatics compared with adult asthmatics. Indeed, we now have evidence that much of the immunopathology is established within the airways of asthmatics very early after the onset of symptoms and, given the lack of correlation with duration of symptoms, may even antedate the first manifestations. There are, however, some differences with neutrophil recruitment being somewhat more prominent than has been recorded from adult observations. The utility of any inflammation parameter in identifying the real future asthmatics has yet to be studied in sufficient detail to define sensitivity, specificity and predictive value. Such studies will be an essential prerequisite to establishing very early intervention strategies, particularly if these involve the use of inhaled and/or oral corticosteroid.

Adult↗