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PubMed2001

Non-invasive positive pressure ventilation for exacerbation of chronic obstructive pulmonary patients in the emergency department.

Patients with acute exacerbation of chronic obstructive pulmonary disease (COPD) commonly present to the emergency department for treatment. Some of them, despite appropriate therapy become more dyspnoeic with increasing acute respiratory failure. The requirement for intubation and mechanical ventilation is for these patients often associated with a prolonged and complicated intensive care unit stay and has been associated with morbidity and mortality rates in excess. Non-invasive ventilation (NIV) emerged recently as a means of reducing those complications. NIV can be a safe and effective means of augmenting ventilation and decreasing inspiratory work in many patients with acute exacerbation of COPD. NIV is generally started in the intensive care unit. Except for a few negative studies, the overall compending studies seem to be in favour of the utilization of NIV in cases of exacerbation of COPD patients. There are few published data on the question whether NIV could or should be started earlier and initiated in the emergency department. It seems that NIV treatment could be an effective addition to standard treatment especially for acute exacerbation of COPD. A more extensive and routine use of non-invasive ventilation in the emergency department requires further study.

Clinical Trials as Topic↗
PubMed2006

Peripheral neuropathy exacerbation associated with topical 5-fluorouracil.

Peripheral neuropathy secondary to 5-flourouracil and capecitabine (Xeloda) has been reported. We report the first case of exacerbation of peripheral neuropathy related to topical 5-flourouracil (Efudex). A 70-year-old Caucasian male with a history of actinic keratosis for 15 years was treated intermittently with topical application of 5-flourouracil. He also developed sensory peripheral neuropathy around the same time, but extensive work-up disclosed no clear etiology. In early 2005, he developed an exacerbation of his peripheral neuropathy following a 21-day course of topical 5-flourouracil for actinic keratosis, especially pain and parasthesias. Dihydropyrimidine dehydrogenase activity was evaluated in the peripheral mononuclear cells both by radioassay and by [2-C] uracil breath test. Dihydropyrimidine dehydrogenase activity was within the normal range by both methods. Stopping topical 5-flourouracil resolved the symptoms to baseline. Instead of topical 5-flourouracil, topical imiquimod was used which did not exacerbate his neuropathy. He was not re-challenged with topical 5-flourouracil. Topical 5-flourouracil has been known to cause mainly dermatological adverse effects, but systemic effects because of absorption are possible, especially in dihydropyrimidine dehydrogenase-deficient patients. As our patient had no other cause responsible for his neuropathy, the onset of symptoms coincided historically with topical application of 5-flourouracil and the 5-flourouracil usage preceded an exacerbation of sensory symptoms, we conclude that this drug was responsible for his polyneuropathy.

Aged↗
PubMed2005

Levalbuterol versus racemic albuterol in the treatment of acute exacerbation of asthma in children.

OBJECTIVE: To compare levalbuterol and racemic albuterol for the treatment of acute exacerbation of asthma in pediatric population. DESIGN: Prospective, double-blind, randomized research trial in a pediatric emergency department of an urban tertiary care hospital. PARTICIPANTS: Children 5 to 21 years with a history of asthma presenting to the emergency department in acute exacerbation. INTERVENTIONS: As per a computer-generated randomization sequence, patients received either 1.25 mg of levalbuterol or albuterol 2.5 mg via nebulization along with ipratropium hydrochloride. Patients received 3 back-to-back treatments as needed every 20 minutes, maximum of 3; 2 mg/kg of oral prednisone was administered to the patients after the second treatment. Baseline respiratory parameters such as oxygen saturations, respiratory rates, and peak flow rates were measured and repeated after every treatment.The decision for further treatments and or hospitalization was made by the treating emergency department physician as per his/her clinical judgement of the respiratory parameters at the end of 3 treatments. RESULTS: Seventy patients completed the study. Most of the patients were in moderate severity of asthma exacerbation. All patients in both groups showed improvement in oxygen saturations, respiratory rates, and peak flow rates. However, no statistically significant difference was observed in the 2 groups regarding the respiratory parameters (P > 0.05). CONCLUSION: Levalbuterol is not more efficacious than racemic albuterol in improving respiratory parameters in children presenting with acute exacerbation of asthma.

Adolescent↗
PubMed1990

The inflammatory response in asthma exacerbation: changes in circulating eosinophils, basophils and their progenitors.

Circulating eosinophils, basophils and eosinophil/basophil (Eo/B) progenitors were examined in 12 patients at the time of an exacerbation of asthma accompanied by sputum eosinophilia and after resolution of the exacerbation with inhaled corticosteroid treatment. Differential counts were performed and peripheral blood non-adherent mononuclear cells were cultured for 14 days in methyl-cellulose to determine the number of Eo/B and granulocyte-macrophage (GM) colonies without knowledge of the clinical conditions or findings. With resolution of the asthma exacerbation on beclomethasone therapy, there were significant falls in circulating eosinophils, basophils and Eo/B colonies whereas GM colonies were unchanged. To elucidate whether the observed changes could be due to systemic absorption or local action of inhaled corticosteroid, seven subjects with allergic rhinitis and no current evidence of lower airway inflammation (no symptoms of asthma and normal methacholine airway responsiveness) received 14 days' treatment with the same dose of inhaled beclomethasone or of placebo in a double-blind randomized cross-over study. No significant changes in airway function or in circulating cell counts were observed. The results suggest reduced production of eosinophils and basophils after the resolution of an exacerbation of asthma. This effect may be due to reduced levels of airway-derived eosinophil-basophil growth and differentiation factors.

Adrenal Cortex Hormones↗
PubMed2005

Persistence of rhinovirus RNA after asthma exacerbation in children.

BACKGROUND: Rhinoviruses (RVs) are believed to cause most asthma exacerbations but their role in the severity of acute asthma and subsequent recovery of airway function is not defined. The importance of atopy in virus-host interactions is also not clear. OBJECTIVE: We postulated that RV infection and atopic skin prick responses influence the severity of asthma exacerbations as measured by peak expiratory flow (PEF). METHODS: Patients aged 4-12 years admitted with acute severe asthma to a hospital emergency room (ER) were recruited. PEF measurements were obtained and nasal aspirates (NA) were taken. Atopy was diagnosed by skin prick responses to allergen and the presence of RV RNA and respiratory syncytial virus (RSV) RNA in NAs was detected using validated PCR assays. Patients were restudied after 6 weeks and after 6 months. RESULTS: Fifty children with acute asthma (mean age+/-SD, 7.4+/-2.7) were enrolled; atopy was present in 37 (74%). RV RNA was detected in 41 (82%) and RSV RNA in six (12%) subjects. After 6 weeks 41 patients were restudied and RV RNA was again detected in 18 (44%). RV RNA was detected after 6 months in four of 16 patients restudied (25%; P=0.008 vs. ER) and in two of nine children from a control group with stable asthma (22%; P=0.009 vs. ER). Overall PEF measurements were reduced in asthmatics admitted to ER (% predicted, 63.4+/-16.4%) but did not differ between patients with RV RNA, RSV RNA or neither virus present. In subjects with RV RNA detectable in ER and after 6 weeks, measurements of PEF in ER were significantly lower than in patients in whom RV RNA was present in ER but absent after 6 weeks (P=0.009). Regression analysis linked persistence of RV RNA, but not skin prick responses to allergen, to severity of PEF reductions in ER. CONCLUSION: RV RNA was detectable in >40% of asthmatic children 6 weeks after an acute exacerbation. Asthma exacerbations were more severe in patients with persistence of RV RNA suggesting that the severity of acute asthma may be linked to prolonged and possibly more severe RV infections.

Acute Disease↗
PubMed1993

Higher anti-heparan sulphate reactivity during systemic lupus erythematosus (SLE) disease exacerbations with renal manifestations; a long term prospective analysis.

Cross-reactive antibodies against heparan sulphate (HS) have been suggested to play a role in initiating renal disease in SLE. Recently, we found that HS-reactivity is mediated by anti-DNA antibodies complexed with DNA and histones. To evaluate the clinical significance of anti-HS reactivity, we studied prospectively a cohort of 72 consecutive SLE patients, of whom 22 experienced 40 exacerbations. In 20 of these exacerbations renal symptoms were present. In these 20 exacerbations significantly higher anti-DNA (median 1:160) and anti-HS (median 1:30) titres were detected compared with exacerbations without renal manifestations (median 1:60 for anti-DNA and negative for anti-HS). There were no correlations with other symptoms of SLE. Anti-HS titres showed a significant correlation with anti-DNA antibody titres (rs = 0.57, P < 0.05). Anti-HS without anti-DNA reactivity was never detected. Some SLE patients showed a high anti-DNA titre without anti-HS reactivity, suggesting that not all anti-DNA antibodies are able to bind to histone/DNA complexes and thus to exhibit anti-HS reactivity. Our findings indicate that anti-HS reactivity is correlated with renal disease in SLE.

Antibodies, Antinuclear↗
PubMed1996

Treatment of severe exacerbation of chronic obstructive pulmonary disease with mask-applied continuous positive airway pressure.

The efficacy of mask-applied continuous positive airway pressure (CPAP) in the treatment of patients with acute severe exacerbations of chronic obstructive pulmonary disease (COPD) was examined. Ten patients with severe exacerbation of COPD who had deteriorated during conventional therapy were treated with face-mask delivered CPAP (+5 cmH2O; Downs Vital signs Inc., New Jersey, USA) instead of tracheal intubation and mechanical ventilation. The patients that were selected required mental alertness, intact upper airway reflexes, the clinical signs of dynamic hyperinflation and a positive end-expiratory pressure auto-(PEEP) manifested as expiratory wheeze and grunting. Nine out of 10 patients responded promptly to mask-CPAP with less distress, better oxygenation, lower respiratory and pulse rates. There was no significant change in arterial carbon dioxide tension with mask-CPAP treatment. One patient deteriorated on mask-CPAP and required intubation and mechanical ventilation. Three patients died (none of these patients died during the acute period of exacerbation). It was concluded that Mask-CPAP may be an alternative to mechanical ventilation in the treatment of selected patients with severe hypercapnic exacerbations of COPD.

Aged↗
PubMed2006

Systemic antioxidant defences during acute exacerbation of chronic obstructive pulmonary disease.

OBJECTIVE AND BACKGROUND: Existence of an increased oxidative stress has been confirmed in patients with acute exacerbation of COPD. This study aims to examine the extent and time-course of antioxidant defence in patients with an acute exacerbation of COPD in comparison with stable patients. METHODS: Twelve patients with acute exacerbation were studied at admission, and then 24 h and 48 h following admission and at discharge. The antioxidants assessed were the endogenous antioxidants: glutathione peroxidase, superoxide dismutase, oxidized and reduced glutathione, albumin and exogenous antioxidants: alpha-tocopherol and retinol. Trolox equivalent antioxidant capacity as a marker of antioxidant status was also measured. RESULTS: There was an increase in glutathione peroxidase and superoxide dismutase 48 h after admission (P<0.05). Alpha-tocopherol was the lowest 24 h after admission and increased significantly at discharge (P<0.05). CONCLUSIONS: There is an increase in antioxidant defence during acute exacerbation of COPD reaching a maximum at 48 h after admission. This rise in the antioxidant defence is not sufficient to prevent depletion of non-enzymatic antioxidants such as alpha-tocopherol.

Aged↗
PubMed2007

Oxidative stress and lipid-derived inflammatory mediators during acute exacerbations of cystic fibrosis.

BACKGROUND AND OBJECTIVE: In cystic fibrosis (CF) very few studies have assessed sputum 8-iso-PGF2alpha levels during pulmonary exacerbations as a direct measure of airway oxidative stress. The role of other lipid-derived inflammatory mediators, such as the cysteinyl leukotrienes (cys-LTs) and prostaglandin (PG)-E2, during exacerbations is also poorly defined and the effect of conventional antibiotic therapy on these components of the inflammatory process is unclear. METHODS: Sputum 8-iso-PGF2alpha, total cys-LT and PGE2 levels were measured in 17 CF patients experiencing a pulmonary exacerbation and repeated analysis were performed in 15 of these patients after antibiotic treatment. Eight stable CF and nine healthy subjects provided control data. RESULTS: Sputum 8-iso-PGF2alpha was significantly elevated in acute, but not stable CF patients versus healthy controls (P < 0.001). Similarly, sputum cys-LT and PGE2 levels were increased in acute compared with stable CF patients and healthy controls (P <or= 0.001). Although substantially lower than in acute patients, sputum cys-LT levels in stable patients were also significantly higher than in normal controls (P = 0.01). There were strong associations between cys-LT levels and sputum total cell counts, and blood neutrophils in acute patients (r2 = 0.53, P = 0.001 and r2 = 0.33, P < 0.05, respectively). Overall in the CF patients, FEV1% predicted was strongly and negatively correlated with sputum 8-iso-PGF2alpha (r2 = 0.34, P = 0.006), cys-LT (r2 = 0.40, P = 0.002) and PGE2 (r2 = 0.52, P < 0.001) levels. Antibiotic treatment reduced sputum total cell count (P = 0.03), but did not affect 8-iso-PGF2alpha, cys-LT or PGE2 levels. CONCLUSIONS: CF exacerbations are characterized by increased oxidative stress and sputum concentrations of bioactive lipid mediators. Treatment does not modulate these aspects of inflammation and more targeted therapy needs further study.

Adolescent↗
PubMed1992

Glucocorticoids exacerbate kainic acid-induced extracellular accumulation of excitatory amino acids in the rat hippocampus.

Glucocorticoids (GCs) compromise the ability of hippocampal neurons to survive various insults, and do so, at least in part, by exacerbating steps in the glutamate/N-methyl-D-aspartate (NMDA)/calcium cascade of damage. As evidence, GCs impair uptake of glutamate by hippocampal astrocytes, the GC endangerment of the hippocampus is NMDA receptor dependent, and GCs exacerbate kainic acid (KA)-induced calcium mobilization. These observations predict that GCs should also exacerbate KA-induced accumulation of extracellular glutamate and aspartate. To test this, adrenalectomized rats were given replacement GCs in either the low or high physiological range. Three days later, rats were anesthetized and 1 mM KA was infused through a dialysis probe placed in the dorsal hippocampus. Extracellular amino acid concentrations in the dialysate were then assessed by HPLC. After KA infusion, high-GC rats (30 +/- 3 micrograms/dl) had significantly elevated concentrations of glutamate and aspartate compared with low-GC rats (all less than 0.95 micrograms/dl). The glutamate accumulation was due to GCs raising pre-KA concentrations, whereas the aspartate accumulation was due to GCs exacerbating the KA-induced rise. Glutamine concentrations were unaffected by KA, whereas the high-GC regimen elevated glutamine concentrations both before and after KA. Taurine concentrations rose after infusion of KA, but were unaffected by GC regime, whereas alanine concentrations were unaffected by either manipulation. Serine concentrations were unaffected by KA, but were depressed both before and after KA in high-GC rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acids↗
PubMedDate not supplied

EEG changes and seizure exacerbation in young children treated with carbamazepine.

Carbamazepine (CBZ) has been reported to exacerbate some seizure types in children. We studied the correlation between CBZ-associated EEG changes and seizure exacerbation in 59 children aged < 6 years treated with CBZ. All patients had EEGs before and after initiation of treatment; initial EEGs were not significantly different among the patients. In 33 children (56%), the subsequent EEGs were either unchanged or improved or demonstrated minor changes (Group I), and excellent to complete seizure control was achieved in 67% of patients. In 26 children (44%), the EEG became significantly more abnormal and was characterized predominantly by new appearance of generalized spike/polyspike-and-wave discharges (group II). The majority of these patients (65%) experienced seizure exacerbation (p < 0.001). For group I, symptomatic partial epilepsy, idiopathic focal epilepsy, and complex febrile seizures were significantly more common; in group II, cryptogenic seizure disorders were more common (p < 0.005). Children in group I were more likely to remain on CBZ or to be weaned from medication after successful treatment, whereas children in group II required additional medication(s) or complete discontinuation of CBZ. Our results suggest that new appearance of generalized paroxysmal discharges after treatment is highly correlated with seizure exacerbation or suboptimal control as well as with adverse outcome. Conversely, absence of significant EEG deterioration on CBZ is usually associated with good seizure control.

Acute Disease↗
PubMed1987

Acute multiple sclerosis exacerbations are characterized by low cerebrospinal fluid suppressor/cytotoxic T-cells.

The present study describes peripheral blood (PB) and CSF T-lymphocyte subpopulations in 55 MS patients with and without acute exacerbation and compares the results with those obtained from 8 with CNS infections and 45 with other neurological disorders or symptoms (OND). The MS patients were most strongly characterized by a decline of their CSF suppressor/cytotoxic T-cells, which was most profound during acute exacerbations. The proportional amount of CSF helper/inducer T-cells (Th) was higher in both MS group than in the OND group, but not different from that of the CNS infection group. No statistically significant change in the CSF Th-cells during exacerbations was seen. MS patients without an exacerbation had somewhat higher levels of their PB Th-cells than the patients with OND, but otherwise no differences in the PB T-cell subsets were seen.

Cerebrospinal Fluid↗
PubMed2006

Effect of high-dose methylprednisolone treatment on CCR5 expression on blood cells in MS exacerbation.

OBJECTIVES: Therapy of acute exacerbations of multiple sclerosis (MS) with high-dose intravenous methylprednisolone (IVMP) has shortened the recovery period after relapses, but the mechanisms responsible for the beneficial effects of IVMP in attacks have not been clearly established. Our purpose was to analyze the effect of IVMP on the expression of chemokine receptor 5 (CCR5) protein in blood in acute MS exacerbation. MATERIALS AND METHODS: Blood samples were collected from 10 patients with an acute MS exacerbation and the levels of CCR5 on CD4(+) and CD8(+) T cells and CD14(+) monocytes were analyzed by using flow cytometry before IVMP, 24 h, 1 and 3 weeks after commencement of treatment. RESULTS: During the 3-week period the percentages of CCR5-expressing CD4(+) T cells and CD8(+) T cells tended to decrease (P = 0.09 and 0.05, respectively), but the effect did not reach statistical significance. No marked changes were found in the percentage of CCR5-expressing CD14(+) cells. CONCLUSIONS: A tendency to a reduction of CCR5-expressing CD4(+) and CD8(+) blood cells induced by IVMP suggests inhibition of their potential to transmigrate into the central nervous system, which is consistent with the short-term beneficial effect of IVMP in acute exacerbation of MS.

Adult↗
PubMed1976

Comparison of cellular and humoral immunity against streptococcal and adult human oral mucosa antigens in relation to exacerbation or recurrent aphthous stomatitis.

Cell-mediated immunity (CMI) and humoral mediated immunity (HMI) against streptococcal and adult human oral mucosa (AHOM) antigens were investigated in patients with inactive and active recurrent aphthous stomatitis (RAS). The CMI and HMI were examined by means of the leucocyte migration test (LMT) and a double layer immunofluorescence (IF) technique. The CMI against Streptococcus sanguis strain 2A, streptococcus pyogenes strain M5, and AHOM was significantly increased in inactive and active RAS. Significant difference between active and inactive RAS was only demonstrated when Strep. 2A was used as antigen in the leucocyte migration cultures. Longitudinal observations in relation to exacerbation of RAS revealed significant changes in the migration indices (MI) when Strep. 2A and AHOM were used as antigens. Extracts of Strep. M5 and other tissues as kidney and uterus did not show any significant changes of MI in relation to the exacerbation of RAS. The IF-investigations detected significantly raised IgG antibodies against washed whole cells of Streptococcus sanguis strain 2A and Streptococcus pyogenes strain M5 in sera from patients with RAS. The autoantibodies in RAS belonged to the immunoglobulin classes IgG and IgM. The detected antibodies were able to blind serum complement (C3). The distribution of endpoint titres (EPT) against Strep. 2A, Strep. M5, and AHOM antigens did not differ significantly in patients with active RAS in relation to those with inactive RAS. Furthermore, the EPT against Strep. 2A and AHOM were not significantly changed in relation to exacerbation of RAS. The present investigations show that CMI and HMI against streptococcal and AHOM antigens are characteristic features of RAS and indicate that the CMI against Strep. 2A and AHOM is significantly increased in relation to exacerbation of RAS.

Antibodies↗
PubMed2006

Risk factors of superinfection following imipenem/cilastatin therapy in hospitalised patients with acute exacerbations of severe chronic obstructive pulmonary disease.

Imipenem is often used in treatment of acute exacerbations of severe chronic obstructive pulmonary disease (COPD). Superinfection following imipenem therapy is a common cause of treatment failure and high economic burden. This study is aimed to explore any clinical factors which determine the risk of superinfection after imipenem treatment in acute exacerbations of severe COPD. A prospective observational study was conducted in a 5-bed respiratory intensive care unit of a Chinese University hospital. Fifty-one patients with acute exacerbations of severe COPD who were hospitalised and treated with imipenem for more than 3 days were enrolled during 1.5 year. The associations between the risk of superinfection and potential factors were analysed by logistic regression. Forty-seven out of 51 patients (92.2%) had their symptoms and signs improved at the end of imipenem treatment. Superinfections were developed in 12 patients, and the superinfection rate was as high as 30.8% (12 out of 39 patients with definite bacteriologic responses). The frequent superinfecting organisms were Stenotrophomonas maltophilia and Pseudomonas aeruginosa. Among a wide range of potential risk factors, we found that lower blood pH, previous cephalosporines treatment and longer period of imipenem treatment are independently associated with a higher risk of superinfection. The risk of superinfection following imipenem treatment in hospitalised patients with acute exacerbations of COPD was high. Lower blood pH, previous cephalosporines treatment and longer period of imipenem treatment all increased the risk of superinfection.

Acute Disease↗
PubMed1995

Production of elastase, exotoxin A, and alkaline protease in sputa during pulmonary exacerbation of cystic fibrosis in patients chronically infected by Pseudomonas aeruginosa.

Secretion of Pseudomonas aeruginosa elastase, exotoxin A, and alkaline protease in sputum during bronchopulmonary exacerbations was examined in 18 cystic fibrosis patients chronically infected with this microorganism. The patients were studied during one or several exacerbation periods necessitating hospitalizations of 12 to 20 days. In all cases, P. aeruginosa was present in bronchial secretions at admission and was not eradicated after treatment. The P. aeruginosa density decreased significantly after antibiotic therapy but remained greater than 10(6) CFU/g of sputum in most cases. Significant amounts of P. aeruginosa exoproteins were measured in total homogenized bronchial secretions by immunoenzymatic assays. The detection of higher levels of exoproteins at admission, the significant decrease after treatment, and the absence of exoproteins during intercrisis phases constituted arguments for a renewal of virulence of P. aeruginosa during exacerbations. Nevertheless, the concomitant changes in bacteria load and the triggering of the inflammatory process and immune complex formation could also contribute to pulmonary exacerbations.

ADP Ribose Transferases↗
PubMed2005

Determinants for the occurrence of acute exacerbation of hepatitis B virus infection in Chinese patients after HBeAg seroclearance.

This study was performed to determine the factors for predicting the occurrence of acute exacerbation of hepatitis B virus infection in HBeAg-negative patients. Two hundred and sixteen patients with known times of HBeAg seroclearance were recruited. Liver biochemistry and virologic markers were monitored. Precore and core promoter mutations were determined by a line probe assay. The median age at HBeAg seroclearance was 34.5 years. The median follow-up duration was 26.4 months. Fifty-six (27.9%) patients had acute exacerbations. By Cox regression analysis, male gender, older age, and core promoter mutations at the time of HBeAg seroclearance were independently associated with the occurrence of acute exacerbation after HBeAg seroclearance (P = 0.025, 0.018, and 0.001, respectively). Fourteen (7.0%) patients had HBeAg seroreversion within a median follow-up period of 11.6 months after HBeAg seroclearance. By Cox regression analysis, older age at HBeAg seroclearance was independently associated with the chance of HBeAg seroreversion (P = 0.01). We concluded that male patients with core promoter mutations and delayed HBeAg seroclearance had a higher cumulative chance of acute exacerbation in the HBeAg-negative phase. Patients with delayed HBeAg seroclearance had a higher frequency of HBeAg seroreversion.

Acute Disease↗
PubMed2005

Systemic administration of the chemokine macrophage inflammatory protein 1alpha exacerbates inflammatory bowel disease in a mouse model.

INTRODUCTION: Exacerbations of inflammatory bowel disease are thought to be related to concurrent infections. As infections are associated with elevated local and serum concentrations of chemokines, we have determined whether systemic administration of the CC chemokine macrophage inflammatory protein 1alpha (MIP-1alpha) exacerbates colitis in a mouse model. METHODS: Colitis was induced in Balb/c mice using trinitrobenzene sulfonic acid (TNBS). Starting four days later, animals received daily intraperitoneal injections of recombinant MIP-1alpha. On day 7, mice were killed and pieces of colon taken for immunohistology and polymerase chain reaction analysis. The direct effects of MIP-1alpha on mucosal T cells and fibroblasts in vitro were also investigated. RESULTS: Systemic administration of MIP-1alpha markedly enhanced colitis with mice developing large transmural ulcers filled with granulation tissue. Treatment resulted in increased numbers of CD4 cells infiltrating the colonic lamina propria, increased interferon gamma (IFN-gamma) levels, and increased transcripts for tumour necrosis factor alpha (TNF-alpha) and matrix metalloproteinase 3 (MMP3). Isolated lamina propria lymphocytes from mice with TNBS colitis contained increased numbers of IFN-gamma and TNF-alpha transcripts when stimulated with MIP-1alpha in vitro. Colonic lamina propria fibroblasts also responded to MIP-1alpha with increased proliferation and decreased collagen 1 synthesis but fibroblast proliferation was not seen in vivo. CONCLUSIONS: These experiments show that increasing serum concentrations of a chemokine, MIP-1alpha, exacerbates immune mediated colitis. The effect seems to be due to the ability of MIP-1alpha to boost Th1 responses in the gut wall. Our findings also suggest a potential pathway by which peripheral infections can exacerbate inflammatory bowel disease.

Animals↗