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J E Repine

Publications and source records attributed to J E Repine.

At least 37 records · Page 2Linked to original sources
PubMed1997

Nitric oxide prevents neutrophil-mediated acute renal failure.

The contribution of nitric oxide (NO) to ischemic acute renal failure is unclear. Because polymorphonuclear neutrophils (PMN) accentuate injury in kidneys subjected to ischemia-reperfusion and because NO has potent vascular and PMN effects, we examined the contribution of NO to PMN-mediated injury in isolated perfused rat kidneys. Nonischemic and ischemic kidneys were perfused by the isolated kidney technique in the presence or absence of PMN and NO agonists [sodium nitroprusside (SNP), L-arginine (L-Arg)] or a NO synthase inhibitor [N omega-nitro-L-arginine (L-NNA)]. In nonischemic kidneys, the NOS antagonist decreased perfusion flow rate by 25% without affecting glomerular filtration rate (GFR) or tubular sodium reabsorption (TNa), whereas NOS agonist treatment had no effects. After 20 min of ischemia/60 min reperfusion in the absence of PMN NO agonist treatment potentiated ischemia-reperfusion-induced loss of GFR and TNa, whereas adding the NO antagonist lessened glomerular and tubular injury. Reperfusion of ischemic kidneys with PMN resulted in PMN retention and potentiated ischemic injury. However, increases in PMN retention as well as decreases in GFR and TNa caused by PMN were prevented by SNP and worsened by L-NNA. Moreover, in nonischemic kidneys, activated PMN caused renal injury and PMN retention, which were prevented by SNP and worsened by L-NNA. In conclusion, 1) NO worsens ischemic injury in the absence of PMN, and 2) NO prevents the PMN component of ischemic renal injury by blocking PMN retention and the deleterious effects of activated PMN on glomerular and tubular function.

Absorption↗
PubMed1997

Endothelial cells protect vascular smooth muscle cells from H2O2 attack.

Endothelial-dependent vascular responses are altered in ischemic acute renal failure. Oxidants formed during reperfusion of ischemic kidneys injure the renal microvasculature and prevent recovery of renal function. To determine whether endothelial cells (EC) modulate oxidant attack on vascular smooth muscle cells (VSMC), rat mesenteric artery VSMC were grown on coverslips and then coincubated with bovine pulmonary artery EC grown in wells. In the absence of EC, H2O2 caused time- and concentration-dependent increases in VSMC injury as indicated by release of [3H]adenine. In contrast, addition of EC reduced H2O2-mediated (5 mM, 1 h) VSMC adenine release from 63.8 +/- 4.5% to 28.6 +/- 2.9% (P < 0.001). The protective effect of EC did not occur when H2O2 was added to the surface of VSMC unopposed to EC and was partially reversed when EC were treated with aminotriazole to inactivate catalase (41.7 +/- 2.7%). To determine whether EC nitric oxide (NO) modified H2O2 attack on VSMC, EC were treated with N omega-nitro-L-arginine (L-NNA). The protective effect of EC was partially abrogated with L-NNA (53.8 +/- 4.3%). Treatment of EC with interleukin-1 beta (IL-1 beta) for 24 h prior to coincubation with VSMC enhanced the protective effect of EC. IL-1 beta-induced protection was reversed with L-NNA. No protection was observed when VSMC were treated with 8-bromoguanosine 3',5'-cyclic monophosphate, forskolin, or phorbol 12-myristate 13-acetate. Our conclusions are as follows. VSMC are protected by EC from luminal but not contraluminal oxidant attack. The protective effect of EC is mediated by catalase- and NO-dependent inactivation of oxidants. EC dysfunction could account for renal injury caused by oxidants formed during reperfusion of ischemic kidneys.

Adenine↗
PubMed1997

Lisofylline prevents leak, but not neutrophil accumulation, in lungs of rats given IL-1 intratracheally.

Interleukin-1 (IL-1) is increased in lung lavages from patients with the acute respiratory distress syndrome, and administering IL-1 intratracheally causes neutrophil accumulation and a neutrophil-dependent oxidative leak in lungs of rats. In the present study, we found that rats pretreated intraperitoneally with lisofylline [(R)-1-(5-hydroxyhexyl)-3, 7-dimethylxanthine (LSF)], an inhibitor of lysophosphatidic acid acyl transferase, which reduces the production of unsaturated phosphatidic acid species, did not develop the lung leak or the related ultrastructural abnormalities that occur after intratracheal administration of IL-1. However, rats pretreated with LSF and then given IL-1 intratracheally did develop the same elevations of lung lavage cytokine-induced neutrophil chemoattractant (CINC) levels and the same increased numbers of lung lavage neutrophils as rats given IL-1 intratracheally. Lungs of rats given IL-1 intratracheally also had increased unsaturated phosphatidic acid and free acyl (linoleate, linolenate) concentrations compared with untreated rats, and these lipid responses were prevented by pretreatment of LSF. Our results reveal that LSF decreases lung leak and lung lipid alterations without decreasing neutrophil accumulation or lung lavage CINC increases in rats given IL-1 intratracheally.

Adjuvants, Immunologic↗
PubMed1997

XO increases neutrophil adherence to endothelial cells by a dual ICAM-1 and P-selectin-mediated mechanism.

Circulating xanthine oxidase (XO) can modify adhesive interactions between neutrophils and the vascular endothelium, although the mechanism underlying this effect are not clear. We found that treatment with XO of bovine pulmonary artery endothelial cells (EC), but not neutrophils or plasma, increased adherence, suggesting that XO had its primary effect on EC. The mechanism by which XO increased neutrophil adherence to EC involved binding of XO to EC and production of H2O2. XO also increased platelet-activating factor production by EC by a H2O2-dependent mechanism. Similarly, the platelet-activating factor-receptor antagonist WEB-2086 completely blocked XO-mediated neutrophil EC adherence. In addition, neutrophil adherence was dependent on the beta 2-integrin Mac-1 (CD11b/CD18) but not on leukocyte functional antigen-1 (CD11a/CD18). Treatment of EC with XO for 30 min did not alter intercellular adhesion molecule-1 surface expression but increased expression of P-selectin and release of von Willibrand factor. Antibodies against P-selectin (CD62) did not affect XO-mediated neutrophil adherence under static conditions but decreased both rolling and firm adhesive interactions under conditions of shear. We conclude that extracellular XO associates with the endothelium and promotes neutrophil-endothelial cell interactions through dual intercellular adhesion molecule-1 and P-selectin ligation, by a mechanism that involves platelet-activating factor and H2O2 as intermediates.

Animals↗
PubMed1997

Endogenous nitric oxide decreases xanthine oxidase-mediated neutrophil adherence: role of P-selectin.

The oxygen radical-producing enzyme xanthine oxidase (XO) can promote neutrophil adherence to endothelium. Recognizing that a balance often exists in inflammatory processes, we sought to determine whether XO initiates antiadherent pathways. We found that bovine pulmonary arterial endothelial cells (EC) exposed to XO released increased amounts of nitrite into the media, reflecting an increased production of nitric oxide (NO). When EC were subjected to shear stress, treatment with XO and/or the NO synthase inhibitor N omega-nitro-L-arginine (L-NNA) increased neutrophil rolling behavior and firm neutrophil adherence to EC in an additive fashion. Both rolling and adherent interactions were abolished by monoclonal antibodies directed against P-selectin. In addition, treatment of EC with XO and/or L-NNA increased both surface expression of P-selectin and release of von Willebrand factor into media. Finally, treatment of EC with the NO donor sodium nitroprusside decreased XO-mediated neutrophil rolling and adherence. We conclude that XO stimulates EC to produce NO and that NO decreases the P-selectin-dependent neutrophil adhesion initiated by XO. Such increases in endogenous NO may constitute an important negative-feedback response to the acute proadhesive effects of XO.

Animals↗
PubMed1997

Serum ferritin as a predictor of the acute respiratory distress syndrome.

We investigated serum ferritin levels as a predictor of the acute respiratory distress syndrome (ARDS) because: (1) proinflammatory cytokines, which are implicated in ARDS, increase ferritin synthesis; and (2) oxidative stress in patients at risk for ARDS might liberate iron from ferritin, accelerating toxic hydroxyl radical (.OH) formation. Serum ferritin levels measured by radioimmunoassay (RIA) were greater in 75 patients at risk for ARDS (women, p < 0.0001; men, p < 0.0001) and 8 patients with ARDS (women, p = 0.001; men, p = 0.0009) than in healthy control subjects. Serum ferritin levels were also greater in female (p = 0.003) and male (p = 0.003) at-risk patients who developed ARDS than in patients who did not develop ARDS. In women, a value exceeding 270 ng/ml predicted ARDS with an 83% sensitivity, 71% specificity, 67% positive, and 86% negative predictive value. In men, a value exceeding 680 ng/ml predicted ARDS with a 60% sensitivity, 90% specificity, 75% positive, and 82% negative predictive value. Serum ferritin levels did not correlate with C-reactive protein levels, were not different in medical or surgical at-risk patients, and were not accounted for by liver disease. Evaluating serum ferritin levels in at-risk patients may help predict the development of ARDS and thereby improve study and treatment of ARDS. Elevated serum ferritin levels may also regulate the participation of iron in the oxidative responses that contribute to ARDS.

Adult↗
PubMed1997

Circulating IL-1ra and IL-10 levels are increased but do not predict the development of acute respiratory distress syndrome in at-risk patients.

Although numerous cytokines, including interleukin (IL)-1, IL-8, and tumor necrosis factor, circulate in critically ill patients at risk for acute respiratory distress syndrome (ARDS), none clearly predict the development of the syndrome. We hypothesized that cytokines, such as IL-1ra, IL-10, and IL-4, which modulate inflammation, might contribute to or reflect the development of acute lung injury. Accordingly, serial levels of IL-1ra and IL-10 were measured in 77 patients who were identifed as being at risk for the development of ARDS. Initial IL-1ra levels were significantly higher (p < 0.0001) in the patients (7.82 [2.29-38.01] ng/ml) than in normal control subjects (0.24 [0.24-0.34] ng/ml) but did not predict the development of ARDS. Initial IL-1ra levels, however, were greater (p = 0.038) in the patients who died (31.95 [3.02-65.06] ng/ml) compared with survivors (6.61 [1.86-29.33] ng/ml). Similarly, IL-10 levels were increased in patients (155 [53.75-318.75] ng/ml) compared with normal control subjects (0 ng/ml) but did not predict the development of ARDS. Like IL-1ra levels, initial IL-10 levels were significantly higher (p = 0.005) in patients who died compared with survivors. IL-4 was not detectable in any of the patient plasma samples measured. Thus, modulators of inflammation are increased in patients at risk for ARDS who die, but do not predict the development of the syndrome.

Adult↗
PubMed1997

Mepacrine decreases lung leak in rats given interleukin-1 intratracheally.

We hypothesized that phospholipase A2 (PLA2) metabolites contribute to the acute, neutrophil-dependent, edematous lung leak that develops after administration of interleukin-1 (IL-1) intratracheally to rats and tested this premise by using mepacrine to inhibit PLA2 activity in vivo. We found that lung PLA2 activity, lung lavage phospholipid content, lung leak index, lung weight gain, and lung lavage protein concentrations were increased in rats given IL-1 intratracheally compared with sham-treated control rats. By comparison, lungs of mecaprine and IL-1-treated rats had decreased PLA2 activity, lavage phospholipid content, leak, weight gain, and lavage protein increases compared with rats given IL-1 intratracheally. Mepacrine treatment also decreased lung neutrophil accumulation, but not lung lavage cytokine-induced neutrophil chemoattractant (CINC) levels, in rats given IL-1 intratracheally. In parallel experiments, mepacrine treatment reduced the adhesion of human neutrophils to IL-1-treated human umbilical vein endothelial cells in vitro. Our results indicate that PLA2 activity participates in the lung neutrophil retention and pulmonary vascular leak that develops in rats given IL-1 intratracheally.

Animals↗
PubMed1997

TNF mediates lung leak, but not neutrophil accumulation, in lungs of rats given IL-1 intratracheally.

Interleukin-1 (IL-1) is increased in lung lavages obtained from patients with acute respiratory distress syndrome, and administering IL-1 intratracheally to rats causes an acute, neutrophil-dependent, oxidative lung leak. We found that rats given IL-1 intratracheally had increased lung lavage fluid tumor necrosis factor (TNF) levels, and that rats treated with TNF binding protein (TNFbp) intravenously did not develop the increased lung leak that occurs after administration of IL-1 intratracheally. In contrast, rats given IL-1 intratracheally and TNFbp intravenously had the same elevations in lung lavage neutrophil accumulation and lung lavage cytokine-induced neutrophil chemoattractant levels as rats given IL-1 intratracheally. Our results show that TNFbp decreases neutrophil-mediated lung leak, but not lung neutrophil accumulation, after administration of IL-1 intratracheally in rats.

Animals↗
PubMed1996

Purification of rat liver xanthine oxidase and xanthine dehydrogenase by affinity chromatography on benzamidine-sepharose.

The oxidase form of xanthine dehydrogenase (XO; EC 1.1.3.22) has been purified approximately 200-fold from rat liver extracts using a three-step process of heat treatment, ammonium sulfate precipitation, and chromatography on benzamidine-Sepharose. The purified enzyme showed only minor contamination when analyzed by gel electrophoresis under either native or sodium dodecyl sulfate (SDS)-denatured conditions and appears to be intact based on its subunit size on SDS-polyacrylamide gel electrophoresis, its N-terminal amino acid sequence, and its ability to be converted to the NAD-dependent dehydrogenase form (XD; EC 1.1.1.204) by incubation with dithiothreitol. Isoelectric focusing analysis showed that the purified enzyme consists of two major, enzymatically active isoforms with average pI values of 6.13 and 6.23 and a minor enzymatically active isoform with an average pl value of 6.07. A similar purification of XD was achieved by preincubating the partially purified oxidase with dithiothreitol prior to affinity chromatography on benzamidine-Sepharose. The effects of benzamidine on the kinetic properties of purified rat XO were characterized at pH 8 and 9 and were compared to those of bovine milk XO. Benzamidine was found to be a weak competitive inhibitor of the purified rat enzyme with Ki values of 30 and 10 mM at pH 8 and 9, respectively. In contrast, the Ki values for benzamidine with bovine XO were more than 10-fold greater. The findings presented in this study show that benzamidine is a competitive inhibitor of XO and that affinity chromatography on benzamidine-Sepharose provides a simple, rapid, and effective means of purifying both the oxidase and dehydrogenase forms of rat XO.

Aldehyde Oxidase↗
PubMed1996

Tumor necrosis factor induced acute lung leak in rats: less than with interleukin-1.

Although local tumor necrosis factor-alpha (TNF) release by alveolar macrophages has been postulated to contribute to the development of acute respiratory distress syndrome (ARDS), the effects of instilling TNF intratracheally on the development of acute lung leak are not known. Our goal was to determine the effect of intratracheally administered TNF on the development of acute lung leak in rats. We found that rats given TNF (500 ng) 5 hours previously intratracheally had increased (p < 0.05) lung lavage cytokine induced neutrophil chemoattractant (CINC) concentrations, lung lavage neutrophils, lung myeloperoxidase (MPO) activity, and lung leak compared to saline-treated control rats. However, all of the responses following TNF instillation were much lower than the responses to interleukin-1 alpha (IL-1) instillation. For example, instilling 50 ng of IL-1 caused 6.4 times the increases in lung lavage CINC concentrations, 15.5 times the increase in lung lavage neutrophils, 3.6 times the increase in lung MPO activity and 3.8 times the increase in lung leak caused by giving 500 ng of TNF intratracheally. Co-treatment with TNF-binding protein decreased both lung MPO and lung leak increases in rats given TNF intratracheally. These observations suggest that locally elevated levels of TNF may induce lung neutrophil recruitment and acute lung leak but that IL-1 is a much more potent agent than TNF in causing lung neutrophil accumulation and lung leak.

Animals↗
PubMed1996

Endothelial cell associated anti-elastolytic activity.

Addition of cultured and then carefully-washed bovine pulmonary artery endothelial cells (EC) decreased (p < 0.05) human neutrophil elastase activity (HNE) in vitro. HNE activity was also decreased (p < 0.05) by addition of histone or protamine treated EC. However, addition of papain or trypsin treated EC decreased HNE activity less than addition of untreated cells suggesting that a protein rather than a difference in cell surface charge was responsible. Other observations suggest that EC anti-elastolytic activity was not due to binding of antiprotease from culture media but was dependent on EC protein synthesis. First, addition of EC grown previously in serum-free media decreased HNE activity the same (p < 0.05) as addition of EC cultured in media containing serum. Second, addition of EC treated beforehand with cycloheximide decreased HNE activity less than (p < 0.05) addition of untreated control EC. We conclude that EC most likely make and have anti-elastolytic activity on their surfaces and speculate that EC associated anti-elastolytic activity may modulate inflammatory, repair and other biologic processes involving neutrophil elastase.

Animals↗
PubMed1996

An increase in serum C18 unsaturated free fatty acids as a predictor of the development of acute respiratory distress syndrome.

OBJECTIVE: No means exist for predicting the acute respiratory distress syndrome (ARDS), which complicates sepsis, trauma, and a variety of clinical disorders. Because activation of phospholipid-signaling pathways involving the acyl chains oleate and linoleate may initiate and amplify the inflammatory response, and thereby lead to the development of ARDS, we examined whether serum concentrations of these bioactive lipids increase and are predictive of ARDS in at-risk patients. DESIGN: Part I: A prospective, single-blind trial. Part II: A prospective, randomized, double-blind trial. SETTING: General intensive therapy units in five university teaching hospitals. SUBJECTS: Part I: Thirty-nine healthy control patients were studied to determine normal distribution of serum acyl values, followed by 30 patients admitted with onset of sepsis, trauma, or development of ARDS (within 24 hrs of admission) over a 1-yr period. Part II: Eight patients admitted with sepsis syndrome over a 2-month period. INTERVENTIONS: Part II: Patients were randomized to receive the substituted methylxanthine, lisofylline (CT1501R), or an identically presented placebo. MEASUREMENTS AND MAIN RESULTS: We measured the serum free fatty acid concentrations in the 39 healthy control subjects, and then we prospectively examined the serum free fatty acid concentrations in 30 age-matched patients in samples obtained within 24 hrs from the onset of sepsis, trauma, or development of ARDS. We then prospectively studied eight septic, at-risk patients who were matched for age, Acute Physiology and Chronic Health Evaluation II scores, Multiple Organ Failure index, and Glasgow Coma Score, in a double-blind, placebo-controlled, pilot study. These patients included four patients who received no treatment and four patients who received lisofylline, a compound that decreases serum unsaturated free fatty acids and diminishes acute lung injury in animals caused by sepsis and/or trauma. The calculated ratios of serum free fatty acids (Le., the ratio of C18 unsaturated fatty acids linoleate and oleate to fully saturated palmitate, C16:0) increased and predicted the development of ARDS in at-risk patients. Serum samples from the 30 patients, obtained within 24 hrs from the onset of sepsis, trauma, or development of ARDS, had significantly increased mean acyl chain ratios (1.42 +/- 0.35 [SD]) compared with healthy control subjects (0.86 +/- 0.25; p < .01). Sera from 13 patients with sepsis or trauma who did not develop ARDS (group A [at-risk, non-pre-ARDS]) also had increased acyl ratios (1.23 +/- 0.27) compared with sera from healthy control subjects (0.86 +/- 0.25; p < .01). Sera from seven patients who subsequently developed ARDS (group B [at-risk, pre-ARDS]) had higher acyl ratios (1.70 +/- 0.21) than group A at-risk patients who did not develop ARDS (1.23 +/- 0.27; p < .01) or healthy control subjects (0.86 +/- 0.25; p < .001). Sera from ten group C patients with ARDS at the time of admission to the study had the highest acyl ratios (1.80 +/- 0.75), which exceeded values for healthy control subjects (p < .001) and group A at-risk patients without ARDS (p = .01), but were not significantly different then group B at-risk, pre-ARDS patients (p = .17). Prospective study of eight septic, at-risk patients demonstrated significantly (p < .05) increased serum acyl ratios in the four untreated patients (findings consistent with the first study) but a significantly (p = .02) reduced ratio in the four at-risk patients treated with lisofyline. CONCLUSIONS: Increases in unsaturated serum acyl chain ratios differentiate between healthy and seriously iII patients, and identify those patients likely to develop ARDS. Thus, the serum acyl ratio may not only prospectively identify and facilitate the assessment of new treatments in patients at highest risk for developing ARDS, but may also lead to new insights about the pathogenesis of ARDS.

Adult↗
PubMed1996

Hemorrhage activates NF-kappa B in murine lung mononuclear cells in vivo.

Hemorrhage rapidly increases the expression of proinflammatory and immunoregulatory cytokines in the lungs. Binding elements for the nuclear transcriptional regulatory factors (NF)-kappa B and NF-IL6 (C/EBP beta) are present in the promoter regions of multiple cytokine genes, including those whose expression is increased after blood loss. In the present experiments, we found increased activation in vivo of NF-kappa B in lung mononuclear cells, but not in splenocytes, taken from mice 1 h after hemorrhage. In contrast, hemorrhage did not activate NF-IL6 in lung cells or splenocytes. Inhibition of xanthine oxidase by prior feeding of a tungsten-enriched diet prevented hemorrhage-induced activation in lung cells of NF-kappa B. Incubating splenocytes in vitro with xanthine oxidase activated NF-kappa B but not NF-IL6. Xanthine oxidase-induced activation of NF-kappa B was inhibited by manganese superoxide dismutase, but not by catalase. These results suggest that xanthine oxidase-mediated superoxide anion-dependent activation of NF-kappa B occurs in vivo and in vitro. This mechanism may contribute to increased lung cytokine responses after hemorrhage.

Animals↗
PubMed1996

Inhaled NO prevents IL-1-induced neutrophil accumulation and associated acute edema in isolated rat lungs.

We determined previously that inhaled nitric oxide (NO) prevented oxidant-dependent capillary leak in isolated rat lungs perfused with human neutrophils and fMLP via a mechanism that was independent of vasodilatation. In the present investigation we determined that inhaled NO (50 ppm) prevented oxidant-dependent acute capillary leak (as reflected by weight gain and Ficoll retention) in isolated rat lungs given human recombinant interleukin-1 alpha (IL-1, 50 ng) intratracheally and perfused with human neutrophils. Inhaled NO also reduced neutrophil migration from the vascular to the airway compartment (as reflected by lung lavage fluid neutrophil numbers and levels of myeloperoxidase), in rats given IL-1 intratracheally and perfused with neutrophils. However, NO did not prevent IL-1-mediated increases in lung lavage levels of cytokine-induced neutrophil chemoattractant (CINC), a potent chemokine produced by alveolar macrophages and other resident cells that mediates IL-1-induced neutrophil infiltration in vivo. We conclude that inhaled NO prevented neutrophil migration and leak caused by intratracheal administration of IL-1 and neutrophil perfusion in isolated rat lungs. We speculate that NO directly inhibits neutrophil responsivity during lung inflammation, a premise that is consistent with the known effects of NO on neutrophil function in vitro. This study provides further evidence that inhaled NO may have important anti-inflammatory as well as vasodilator effects in acute lung injury.

Acute Disease↗
PubMed1995

Phosphatidic acid signaling mediates lung cytokine expression and lung inflammatory injury after hemorrhage in mice.

Because phosphatidic acid (PA) pathway signaling may mediate many basic reactions involving cytokine-dependent responses, we investigated the effects of CT1501R, a functional inhibitor of the enzyme lysophosphatidic acid acyltransferase (LPAAT) which converts lysophosphatidic acid (Lyso-PA) to PA. We found that CT1501R treatment not only prevented hypoxia-induced PA increases and lyso-PA consumption in human neutrophils, but also prevented neutrophil chemotaxis and adherence in vitro, and lung injury and lung neutrophil accumulation in mice subjected to hemorrhage and resuscitation. In addition, CT1501R treatment prevented increases in mRNA levels and protein production of a variety of proinflammatory cytokines in multiple lung cell populations after blood loss and resuscitation. Our results indicate the fundamental role of PA metabolism in the development of acute inflammatory lung injury after blood loss.

Acyltransferases↗
PubMed1995

Interleukin-1 beta-induced neutrophil recruitment and acute lung injury in hamsters.

Administering recombinant interleukin-1 beta (IL-1 beta) intratracheally caused lung neutrophil accumulation and lung injury in hamsters. The percentage of leukocytes that were neutrophils increased progressively in lavages from lungs of hamsters given 25, 50, or 100 ng IL-1 beta intratracheally 2 h before. Lung injury, reflected by increased lung lavage protein concentrations and lung lavage hemoglobin concentrations, increased 2 h after administering 100 ng IL-1 beta. Lung injury, reflected by lung wet weight/body weight ratios, followed similar patterns, with significant increases occurring 2 h after insufflating 50 or 100 ng IL-1. Our results indicate that increased concentrations of IL-1 beta in lung airways can cause neutrophil recruitment and lung injury in hamsters. This mechanism may contribute to the development of lung neutrophil accumulation and lung injury that characterizes ARDS patients who have increased airway levels of IL-1 beta.

Acute Disease↗