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E Abraham

Publications and source records attributed to E Abraham.

At least 19 recordsLinked to original sources
PubMed2002

Wide-field optical coherence tomography: imaging of biological tissues.

We describe a two-dimensional optical coherence tomography technique with which we were able to obtain multiple longitudinal slices of a biological sample directly in a single Z scan. The system is based on a femtosecond Cr4+:forsterite laser and an infrared camera for wide-field imaging of the sample with a depth resolution of 5 microm. With this imaging apparatus we were able to investigate human skin and mouse ear samples and to observe the different constitutive tissues.

Animals↗
PubMed2002

Apoptotic index: use in predicting recurrence in breast cancer patients.

Apoptosis maintains tissue homeostasis through its ability to control cell population and has been extensively studied in human cancers. Relation of apoptosis to prognosis is still controversial. In this study, we analyzed the prognostic significance of apoptotic and mitotic indices (AI & MI) using hematoxylin and eosin stained slides by light microscopy in breast cancer patients. In our study, apoptotic index was significantly associated with predicting relapse free survival (RFS), distant recurrence free survival (DRFS) and overall survival (OS) with lesions having higher apoptotic index showing poor prognosis. Our results also point out that quantitation of apoptotic index by simple light microscopy as a routine practice along with histological diagnosis, could provide additional prognostic information in patients who are at high risk of developing recurrence with breast cancers.

Adenocarcinoma, Mucinous↗
PubMed2002

Nm23H1 and p53 proteins are differentially correlated to metastasis in breast carcinoma.

The prognostic significance of nm23H1 and p53 proteins as predictors of nodal involvement and distant recurrence was evaluated in 63 cancer and 47 benign lesions of the breast. Assessment was carried out by immunohistochemical staining using nm23H1 and p53 antibodies. Results show no relation of nm23H1 either to the malignant nature when compared to benign lesions or to the nodal status. P53 protein, on the other hand, showed significantly increased expression in malignant lesions (p=0.001) and correlated well with nodal positivity (p=0.03). A follow-up study of 5 years showed that among the cases showing recurrence, those with positive mn23H1 showed a shorter distant recurrence free survival (DRFS, p=0.01), while p53 expression had no effect. This result did not agree with the previous reports showing nm23H1 as an antimetastatic gene. This is the first report of positive correlation between nm231-11 and distant recurrence in breast cancers, though such a correlation was reported earlier in certain other cancers. Since nm23H1 is an NDP kinase, having more involvement in signal transduction of cell proliferation, it is not difficult to comprehend such a role for nm23H1 during recurrence. Combining the expression of both proteins, lesions positive for both p53 and nm23H1 had significantly reduced distant recurrence free survival (DRFS), when compared to those negative for both proteins (p=0.0006). It can be concluded that nni23H1 alteration has a potential in predicting DRFS, while p53 alteration has the potential to predict lymph node involvement.

Breast Neoplasms↗
PubMed2001

Role of NF-kappaB in endotoxemia-induced alterations of lung neutrophil apoptosis.

Acute lung injury is frequently associated with endotoxemia and is characterized by the accumulation in the lungs of large numbers of neutrophils activated to produce proinflammatory mediators. In the setting of acute lung injury, the percentage of apoptotic cells among lung neutrophils is decreased. The transcriptional regulatory factor NF-kappaB is activated in neutrophils and other pulmonary cell populations after endotoxemia and appears to play a central role in the development of the acute inflammatory process that leads to lung injury. Because NF-kappaB can modulate apoptosis through increasing expression of anti-apoptotic proteins, activation of NF-kappaB may contribute to the alterations in lung neutrophil apoptosis associated with acute lung injury. In the present experiments, endotoxemia resulted in decreased apoptosis and increased expression of anti-apoptotic mediators among lung neutrophils. Amounts of A1, A20, and Bcl-x(L), anti-apoptotic proteins whose transcription is dependent on NF-kappaB, were increased in lung neutrophils after endotoxemia. Inhibition of nuclear translocation of NF-kappaB increased the percentage of apoptotic lung neutrophils after endotoxemia, but not back to the levels found in unmanipulated animals. Although inhibition of nuclear translocation of NF-kappaB prevented endotoxemia-induced increases in Bcl-x(L), A1, and A20 in lung neutrophils, this intervention did not prevent endotoxemia-associated elevation of Mcl-1, an anti-apoptotic protein primarily under the transcriptional regulation of CREB. These results demonstrate that mechanisms independent of NF-kappaB activation play an important role in modulating lung neutrophil apoptosis after endotoxemia.

Active Transport, Cell Nucleus↗
PubMed2001

Involvement of phosphoinositide 3-kinases in neutrophil activation and the development of acute lung injury.

Activated neutrophils contribute to the development and severity of acute lung injury (ALI). Phosphoinositide 3-kinases (PI3-K) and the downstream serine/threonine kinase Akt/protein kinase B have a central role in modulating neutrophil function, including respiratory burst, chemotaxis, and apoptosis. In the present study, we found that exposure of neutrophils to endotoxin resulted in phosphorylation of Akt, activation of NF-kappaB, and expression of the proinflammatory cytokines IL-1beta and TNF-alpha through PI3-K-dependent pathways. In vivo, endotoxin administration to mice resulted in activation of PI3-K and Akt in neutrophils that accumulated in the lungs. The severity of endotoxemia-induced ALI was significantly diminished in mice lacking the p110gamma catalytic subunit of PI3-K. In PI3-Kgamma(-/-) mice, lung edema, neutrophil recruitment, nuclear translocation of NF-kappaB, and pulmonary levels of IL-1beta and TNF-alpha were significantly lower after endotoxemia as compared with PI3-Kgamma(+/+) controls. Among neutrophils that did accumulate in the lungs of the PI3-Kgamma(-/-) mice after endotoxin administration, activation of NF-kappaB and expression of proinflammatory cytokines was diminished compared with levels present in lung neutrophils from PI3-Kgamma(+/+) mice. These results show that PI3-K, and particularly PI3-Kgamma, occupies a central position in regulating endotoxin-induced neutrophil activation, including that involved in ALI.

Animals↗
PubMed2001

Extracellular superoxide dismutase attenuates lung injury after hemorrhage.

Reperfusion of the lung after hemorrhage generates free radicals such as superoxide (O(2)(.)) that may injure the lung; however, the relative importance of intracellular versus extracellular free radicals is unclear. The superoxide dismutases (SOD) are the primary enzymatic method to reduce superoxide. We examined whether lung-specific overexpression of extracellular superoxide dismutase (EC-SOD) would attenuate hemorrhage-induced lung injury. Wild-type mice and mice overexpressing the human EC-SOD gene with a lung-specific promoter were hemorrhaged by removing 30% of blood volume. After hemorrhage, the lung wet to dry weight ratios increased from 5.4 +/- 0.11 in unmanipulated control mice to 6.3 +/- 0.16 in wild-type mice, but to only 5.60 +/- 0.17 in the EC-SOD transgenic mice (p < 0.05 compared with hemorrhaged wild-type). Hemorrhage-induced lipid peroxidation, as assessed by lung F(2) isoprostanes, was lower in the EC-SOD transgenic mice (3.4 +/- 0.3 microg/lung) compared with wild-type mice (1.9 +/- 0.2 microg/lung; p < 0.05). Compared with wild-type, EC-SOD transgenic mice had attenuated the hemorrhage-induced increase in both pulmonary nuclear factor kappa B (NK-kappaB) activation (relative absorbance 1.1 +/- 0.2 for EC-SOD transgenic versus 2.5 +/- 0.1 for wild-type; p < 0.05) and myeloperoxidase activity (5.1 +/- 0.87 units/g for EC-SOD transgenic versus 11.3 +/- 1.8 units/g for wild-type; p < 0.01). Thus, overexpression of pulmonary EC-SOD in the mouse lung attenuates lung injury after hemorrhage.

Animals↗
PubMed2001

Prevention of influenza and pneumococcal pneumonia in Canadian long-term care facilities: how are we doing?

BACKGROUND: Influenza and pneumococcal pneumonia are serious health problems among elderly people and a major cause of death in long-term care facilities. We describe the results of serial surveys of vaccination coverage and influenza outbreak management in Canadian long-term care facilities over the last decade. METHODS: Cross-sectional surveys consisting of questionnaires mailed to all Canadian residential long-term care facilities for elderly people in 1991 and to a random sample of respondents in 1995 and 1999. RESULTS: The response rates were 83% (430/515) in 1995 and 75% (380/506) in 1999. In 1999 the mean reported rates of influenza vaccination were 83% among residents and 35% among staff, and the mean rate of pneumococcal vaccination among residents was 71%; all 3 rates were significantly higher than those in 1991. The rates were also higher in facilities with an infection control practitioner than in those without such an individual (88% v. 82% for influenza vaccination among residents [p < 0.001], 42% v. 35% for influenza vaccination among staff [p = 0.008] and 75% v. 63% for pneumococcal vaccination among residents [p < 0.001]). Obtaining consent for vaccination on admission to the facility was associated with higher influenza and pneumococcal vaccination rates among residents (p = 0.04 and p < 0.001 respectively). Facilities with higher influenza vaccination rates among residents and staff reported lower rates of influenza outbreaks (p = 0.08 and 0.03 respectively). Despite recommendations from the National Advisory Committee on Immunization, only 50% of the facilities had policies for amantadine prophylaxis during influenza A outbreaks. Amantadine was judged effective in controlling 76% of the influenza A outbreaks and was discontinued because of side effects in 3% of the residents. INTERPRETATION: Influenza and pneumococcal vaccination rates among residents and staff in Canadian long-term care facilities have increased over the last decade but remain suboptimal. Vaccination of residents and staff against influenza is associated with a reduced risk of influenza outbreaks. Amantadine is effective in controlling influenza outbreaks in long-term care facilities.

Aged↗
PubMed2001

Activation of extracellular signal-regulated kinases, NF-kappa B, and cyclic adenosine 5'-monophosphate response element-binding protein in lung neutrophils occurs by differing mechanisms after hemorrhage or endotoxemia.

Acute lung injury is frequently associated with sepsis or blood loss and is characterized by a proinflammatory response and infiltration of activated neutrophils into the lungs. Hemorrhage or endotoxemia result in activation of cAMP response element-binding protein (CREB) and NF-kappa B in lung neutrophils as well as increased expression of proinflammatory cytokines, such as TNF-alpha and macrophage-inflammatory peptide-2, by these cells. Activation of the extracellular regulated kinase (ERK) pathway occurs in stress responses and is involved in CREB activation. In the present experiments, hemorrhage or endotoxemia produced increased activation of mitogen-activated protein kinase kinase (MEK)1/2 and ERK2 (p42), but not of ERK1 (p44), in lung neutrophils. ERK1, ERK2, and MEK1/2 were not activated in peripheral blood neutrophils after hemorrhage or endotoxemia. Inhibition of xanthine oxidase led to further increase in the activation of MEK1/2 and ERK2 in lung neutrophils after hemorrhage, but not after endotoxemia. Alpha-adrenergic blockade before hemorrhage resulted in increased activation in lung neutrophils of MEK1/2, ERK1, ERK2, and CREB, but decreased activation of NF-kappa B. In contrast, alpha-adrenergic blockade before endotoxemia was associated with decreased activation of MEK1/2, ERK2, and CREB, but increased activation of NF-kappa B. Beta-adrenergic blockade before hemorrhage did not alter MEK1/2 or ERK1 activation in lung neutrophils, but decreased activation of ERK2 and CREB, while increasing activation of NF-kappa B. Beta-adrenergic inhibition before endotoxemia did not affect activation of MEK1/2, ERK1, ERK2, CREB, or NF-kappa B. These data indicate that the pathways leading to lung neutrophil activation after hemorrhage are different from those induced by endotoxemia.

Adrenergic alpha-Antagonists↗
PubMed2001

Role of p38 MAP kinase in the development of acute lung injury.

Acute lung injury (ALI) is characterized by an intense pulmonary inflammatory response, in which neutrophils play a central role. The p38 mitogen-activated protein kinase pathway is involved in the regulation of stress-induced cellular functions and appears to be important in modulating neutrophil activation, particularly in response to endotoxin. Although p38 has potent effects on neutrophil functions under in vitro conditions, there is relatively little information concerning the role of p38 in affecting neutrophil-driven inflammatory responses in vivo. To examine this issue, we treated mice with the p38 inhibitor SB203580 and then examined parameters of neutrophil activation and acute lung injury after hemorrhage or endotoxemia. Although p38 was activated in lung neutrophils after hemorrhage or endotoxemia, inhibition of p38 did not decrease neutrophil accumulation in the lungs or the development of lung edema under these conditions. Similarly, the increased production of proinflammatory cytokines and activation of NF-kappaB in lung neutrophils induced by hemorrhage or endotoxemia was not diminished by p38 inhibition. These results indicate that p38 does not have a central role in the development of ALI after either hemorrhage or endotoxemia.

Animals↗
PubMed2001

Cadherins as predictive markers of nodal metastasis in breast cancer.

Adhesion molecules, particularly cadherins play a pivotal role in cancer invasion and metastasis. Because the therapeutic management of tumors with and without nodal metastasis differs considerably, our idea was to identify tumors with metastatic potential. We studied the expression of E-cadherin and P-cadherin immunohistochemically in 51 cases of breast cancer that included 29 node-negative and 22 node-positive cases. Expression of the cadherins was mainly membranous, with cytoplasmic staining in a few lesions. Both E-cadherin and P-cadherin showed significant down-regulation of their expression in node-positive tumors in comparison to node-negative tumors. Logistic regression analysis revealed that the positive expression of E-cadherin and P-cadherin showed low odds ratios of 0.1 and 0.2, respectively, and were statistically significant. On multivariate analysis, both the cadherins were found to be of independent prognostic value. This suggests that cadherin expression could be a marker of nodal metastasis. An observation of interest was that the expression of E-cadherin and P-cadherin were highly correlated (correlation coefficient = 0.5873), which requires further evaluation for confirmation of a common regulatory pathway that could be activated in the early onset of nodal metastasis.

Adenocarcinoma↗
PubMed2001

Lenercept (p55 tumor necrosis factor receptor fusion protein) in severe sepsis and early septic shock: a randomized, double-blind, placebo-controlled, multicenter phase III trial with 1,342 patients.

OBJECTIVE: Phase III study to confirm a trend observed in a previous phase II study showing that a single dose of lenercept, human recombinant p55 tumor necrosis factor receptor-immunoglobulin G1 (TNFR55-IgG1) fusion protein, decreased mortality in patients with severe sepsis or early septic shock. DESIGN: Multicenter, double-blind, phase III, placebo-controlled, randomized study. SETTING: A total of 108 community and university-affiliated hospitals in the United States (60), Canada (6) and Europe (42). PATIENTS: A total of 1,342 patients were recruited who fulfilled the entry criteria within the 12-hr period preceding the study drug administration. INTERVENTION: After randomization, an intravenous dose of 0.125 mg/kg lenercept or placebo was given. The patient was monitored for up to 28 days, during which standard diagnostic, supportive, and therapeutic care was provided. MEASUREMENTS AND MAIN RESULTS: The primary outcome measure was 28-day all-cause mortality. Baseline characteristics were as follows: a total of 1,342 patients were randomized; 662 received lenercept and 680 received placebo. The mean age was 60.5 yrs (range, 17-96 yrs); 39% were female; 65% had medical admissions, 8% had scheduled surgical admissions, and 27% had unscheduled surgical admissions; 73% had severe sepsis without shock, and 27% had severe sepsis with early septic shock. Lenercept and placebo groups were similar at baseline with respect to demographic characteristics, simplified acute physiology score II-predicted mortality, profiles of clinical site of infection and microbiological documentation, number of dysfunctioning organs, and interleukin-6 (IL-6) plasma concentration. Lenercept pharmacokinetics were similar in severe sepsis and early septic shock patients. Tumor necrosis factor was bound in a stable manner to lenercept as reflected by the accumulation of total serum tumor necrosis factor alpha concentrations. There were 369 deaths, 177 on lenercept (27% mortality) and 192 on placebo (28% mortality). A one-sided Cochran-Armitage test, stratified by geographic region and baseline, predicted 28-day all-cause mortality (simplified acute physiology score II), gave a p value of .141 (one-sided). Lenercept treatment had no effect on incidence or resolution of organ dysfunctions. There was no evidence that lenercept was detrimental in the overall population. CONCLUSION: Lenercept had no significant effect on mortality in the study population.

APACHE↗
PubMed2001

Assessment of the safety of recombinant tissue factor pathway inhibitor in patients with severe sepsis: a multicenter, randomized, placebo-controlled, single-blind, dose escalation study.

OBJECTIVE: To identify a safe and potentially effective recombinant tissue factor pathway inhibitor (rTFPI) dose for further clinical evaluation in patients with severe sepsis. DESIGN: Prospective, randomized, single-blind, placebo-controlled, dose escalation, multicenter, multinational phase II clinical trial. SETTING: Thirty-eight intensive care units in the United States and Europe. PATIENTS: Two hundred and ten subjects with severe sepsis who received standard supportive care and antimicrobial therapy. INTERVENTIONS: Subjects received a continuous intravenous infusion of placebo or rTFPI at 0.025 or 0.05 mg/kg/hr for 4 days (96 hrs). MEASUREMENTS AND MAIN RESULTS: There were no significant imbalances in demographics, severity of illness, or source of infection in patients randomized to placebo or either dose of rTFPI. A 20% relative reduction in 28-day all-cause mortality was observed when all rTFPI-treated patients were compared with all placebo patients. An improvement in pulmonary organ dysfunction score and in a composite intensive care unit score (pulmonary, cardiovascular, and coagulation) were also noted in the rTFPI-treated patients. Logistic regression modeling indicated a substantial treatment by baseline laboratory international normalized ratio (INR) interaction effect when only treatment and INR were in the model (p =.037) and when baseline Acute Physiology and Chronic Health Evaluation (APACHE II) and log10 interleukin 6 were adjusted for (p =.026). This interaction effect indicates that higher baseline INR is associated with a more pronounced beneficial rTFPI effect. There was no increase in mortality in subjects treated with either dose of rTFPI compared with placebo. Biological activity, as detected by a statistically significant reduction in thrombin-antithrombin complexes (TATc), was noted in the all rTFPI-treated patients compared with those receiving placebo. There were no major imbalances across all treatment groups with respect to safety. The frequency of adverse events (AEs) and severe adverse events (SAEs) was similar among the treatment groups, with a slight increase in SAEs and SAEs involving bleeding in the 0.05 mg/kg/hr rTFPI group. The overall incidence of AEs involving bleeding was 28% of patients in the all placebo group and 23% of patients in the all rTFPI-treated group; a slight but statistically insignificant increase in incidence of SAEs involving bleeding was observed in the all rTFPI group (9%) as compared with the all placebo group (6%; p =.39). CONCLUSIONS: Although the trial was not powered to show efficacy, a trend toward reduction in 28-day all-cause mortality was observed in the all rTFPI group compared with all placebo. This study demonstrates that rTFPI doses of 0.025 and 0.05 mg/kg/hr could be safely administered to severe sepsis patients. Additionally, rTFPI demonstrated bioactivity, as shown by reduction in TATc complexes and interleukin-6 levels. These findings warrant further evaluation of rTFPI in an adequately powered, placebo controlled, randomized trial for the treatment of severe sepsis.

APACHE↗
PubMed2001

Pharmacokinetics of levofloxacin and ciprofloxacin during continuous renal replacement therapy in critically ill patients.

The pharmacokinetics of intravenously administered levofloxacin and ciprofloxacin were studied in intensive care unit patients during continuous venovenous hemofiltration (CVVH; four patients received levofloxacin, and five received ciprofloxacin) or hemodiafiltration (CVVHDF; six patients received levofloxacin, and five received ciprofloxacin). Levofloxacin clearance was substantially increased during both CVVH and CVVHDF, while ciprofloxacin clearance was affected less. The results of this study suggest that doses of levofloxacin of 250 mg/day and ciprofloxacin of 400 mg/day are sufficient to maintain effective drug concentrations in the plasma of patients undergoing CVVH or CVVHDF.

Adult↗
PubMed2001

Pharmacokinetics of cefepime during continuous renal replacement therapy in critically ill patients.

The pharmacokinetics of cefepime were studied in 12 adult patients in intensive care units during continuous venovenous hemofiltration (CVVH) or continuous venovenous hemodiafiltration (CVVHDF) with a Multiflow60 AN69HF 0.60-m(2) polyacrylonitrile hollow-fiber membrane (Hospal Industrie, Meyzieu, France). Patients (mean age, 52.0 +/- 13.0 years [standard deviation]; mean weight, 96.7 +/- 18.4 kg) received 1 or 2 g of cefepime every 12 or 24 h (total daily doses of 1 to 4 g/day) by intravenous infusion over 15 to 30 min. Pre- and postmembrane blood (serum) samples and corresponding ultrafiltrate or dialysate samples were collected 1, 2, 4, 8, and 12 or 24 h (depending on dosing interval) after completion of the drug infusion. Drug concentrations were measured using validated high-performance liquid chromatography methods. Mean systemic clearance (CL(S)) and elimination half-life (t(1/2)) of cefepime were 35.9 +/- 6.0 ml/min and 12.9 +/- 2.6 h during CVVH versus 46.8 +/- 12.4 ml/min and 8.6 +/- 1.4 h during CVVHDF, respectively. Cefepime clearance was substantially increased during both CVVH and CVVHDF, with membrane clearance representing 40 and 59% of CL(S), respectively. The results of this study confirm that continuous renal replacement therapy contributes substantially to total CL(S) of cefepime and that CVVHDF appears to remove cefepime more efficiently than CVVH. Cefepime doses of 2 g/day (either 2 g once daily or 1 g twice daily) appear to achieve concentrations adequate to treat most common gram-negative pathogens (MIC <or= 8 microg/ml) during CVVH or CVVHDF.

Adult↗
PubMed2001

Interactions between CBP, NF-kappaB, and CREB in the lungs after hemorrhage and endotoxemia.

The transcriptional regulatory factor nuclear factor (NF)-kappaB has a central role in modulating expression of proinflammatory mediators that are important in acute lung injury. In vitro studies have shown that competition between NF-kappaB and cAMP response element binding protein (CREB) for binding to the coactivator CREB-binding protein (CBP) is important in regulating transcriptional activity of these factors. In the present study, we examined in vivo interactions between CBP, CREB, and NF-kappaB in hemorrhage- or endotoxemia-induced acute lung injury. Association of CBP with CREB or the p65 subunit of NF-kappaB increased in the lungs after hemorrhage or endotoxemia. Inhibition of xanthine oxidase before hemorrhage, but not before endotoxemia, decreased p65-CBP interactions while increasing those between CREB and CBP. These alterations in CREB-CBP and p65-CBP interactions were functionally significant because xanthine oxidase inhibition before hemorrhage resulted in increased expression of the CREB-dependent gene c-Fos and decreased expression of macrophage inflammatory protein-2, a NF-kappaB-dependent gene. The present results show that the coactivator CBP has an important role in modulating transcription in vivo under clinically relevant pathophysiological conditions.

Animals↗
PubMed2001

A low level of TNF-alpha mediates hemorrhage-induced acute lung injury via p55 TNF receptor.

Acute lung injury after hemorrhagic shock (HS) is associated with the expression of tumor necrosis factor (TNF)-alpha in the lung. However, the role of TNF-alpha and its receptors in this pulmonary disorder remains obscure. This study examined the temporal relationship of pulmonary TNF-alpha production to neutrophil accumulation during HS and determined the role of TNF-alpha in neutrophil accumulation and lung leak. HS was induced in mice by removal of 30% of total blood volume. Lung TNF-alpha was measured by ELISA. Neutrophil accumulation was detected by immunofluorescent staining, and microvascular permeability was assessed using Evans blue dye. Although HS induced a slight and transient increase in lung TNF-alpha, neutrophil accumulation preceded the increase in TNF-alpha. However, lung neutrophil accumulation and lung leak were abrogated in TNF-alpha knockout mice, and both were restored by administration of recombinant TNF-alpha to TNF-alpha knockout mice before HS. Neutrophil accumulation and lung leak were abrogated in mice lacking the p55 TNF-alpha receptor, but neither was influenced by p75 TNF-alpha receptor knockout. This study demonstrates that a low level of pulmonary TNF-alpha is sufficient to mediate HS-induced acute lung injury during HS and that the p55 TNF-alpha receptor plays a dominant role in regulating the pulmonary inflammatory response to HS.

Acute Disease↗
PubMed2000

HMG-1 as a mediator of acute lung inflammation.

Acute inflammatory lung injury is often a delayed complication of critical illness and is associated with increased mortality. High mobility group-1 (HMG-1) protein, in addition to its role as a transcriptional regulatory factor, has recently been identified as a late mediator of endotoxin lethality. In the present studies, HMG-1 given intratracheally produced acute inflammatory injury to the lungs, with neutrophil accumulation, the development of lung edema, and increased pulmonary production of IL-1beta, TNF-alpha, and macrophage-inflammatory protein-2. In endotoxin-induced acute lung inflammation, administration of anti-HMG-1 Abs either before or after endotoxin exposure decreased the migration of neutrophils to the lungs as well as lung edema. These protective effects of anti-HMG-1 were specific, because pulmonary levels of IL-1beta, TNF-alpha, or macrophage-inflammatory protein-2 were not decreased after therapy with anti-HMG-1. Together, these findings indicate that HMG-1 is a distal mediator of acute inflammatory lung injury.

Adjuvants, Immunologic↗