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ABSTRACT: In comparison with neutrophil-mediated lung diseases, such as acute respiratory distress syndrome, the involvement of IL-8 in lymphocyte-mediated lung diseases has not been fully investigated. Several reports have shown a slight increase in bronchoalveolar lavage fluid (BALF) IL-8 in patients with hypersensitivity pneumonitis (HP) and sarcoidosis (SAR), but the source of the IL-8 has not been clarified. In the present study, the in vivo production of IL-8 by alveolar macrophages (AMs) is examined in these patients by analyzing the cell-associated IL-8, using the flow cytometric method adopted previously. The IL-8 levels in the epithelial lining fluid (ELF) were also assessed. Initially, slight, but significant, increased levels of ELF IL-8 in HP and SAR were confirmed. Using flow cytometric analysis, a significant increase was found in the cell-associated IL-8 of the freshly isolated AMs in HP, but not in SAR, indicating in vivo production of IL-8 by AMs in HP. The cell-associated IL-8 of the AMs cultured with or without lipopolysaccharide was also analyzed. However, in contrast to previous findings in patients with idiopathic pulmonary fibrosis, no differences were found between SAR and HP patients and control subjects. Based on these findings, it is speculated that ELF IL-8 levels are slightly increased in HP and SAR, and they may contribute to the accumulation of neutrophils and possibly lymphocytes. However, the source of IL-8 may be different and AMs are the candidate source of IL-8 in HP, but not in SAR. The flow cytometric method may be useful in assessing cytokines production by AMs.
Scandinavian Journal of Clinical and Laboratory Investigation 02/2004; 64(3):237-43. · 1.38 Impact Factor
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Applied Surface Science 01/2003; 203-204:152-155. · 2.10 Impact Factor
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ABSTRACT: The gene expression profile of CCR3 ligands, eotaxin, RANTES, and monocyte chemoattractant protein-3 (MCP-3), was examined in normal and inflamed guinea pig lungs.
Male Hartley guinea pigs (n = 49).
Pulmonary mRNA was obtained from naive animals, animals treated with intravenous lipopolysaccharide administration, and animals repeatedly exposed to aerosolized allergen (ovalbumin). Northern analysis was performed to quantify pulmonary expression of eotaxin, RANTES, and MCP-3 mRNA. Pulmonary eosinophil peroxidase (EPO) activity was measured to quantify eosinophil accumulation.
Eotaxin and RANTES mRNAs, but not MCP-3 mRNA, were constitutively expressed in guinea pig lungs. Lipopolysaccharide treatment increased MCP-3 mRNA expression, but not eotaxin or RANTES mRNA. In contrast, allergen exposure in sensitized animals caused an increase in eotaxin mRNA, which demonstrated good temporal and quantitative correlation with pulmonary EPO activity, but not in MCP-3 or RANTES mRNA.
Guinea pig CCR3 ligands demonstrated different gene expression profiles in normal and inflamed airways, suggesting that they play different physiological and pathophysiological roles in the airway.
Inflammation Research 01/2002; 50(12):625-30. · 2.11 Impact Factor
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K Fukunaga,
K Asano,
X Q Mao,
P S Gao,
M H Roberts,
T Oguma,
T Shiomi, M Kanazawa,
C N Adra,
T Shirakawa,
J M Hopkin,
K Yamaguchi
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ABSTRACT: Whole genome scan analyses have revealed that chromosomal region 3p21-24, which contains a gene cluster of CC chemokine receptors such as CCR3, is possibly linked to asthma. Because CCR3 ligands play a pivotal role in the selective recruitment and activation of inflammatory cells in the asthmatic airway, the authors examined whether there is any association between asthma and the CCR3 gene polymorphisms. Three polymorphisms were identified using the single stranded conformational polymorphism method in Japanese (Asian) and British (Caucasian) subjects; one silent mutation T51C and two missense mutations G824A and T971C. These polymorphisms were examined in 391 Japanese subjects (210 asthmatics and 181 nonasthmatic controls) and 234 British subjects (142 asthmatics and 92 nonasthmatic controls). Asthma diagnosis was based on episodic symptoms, documented wheeze, and the presence of reversible airflow limitation. CCR3 T51C demonstrated a significant association with the diagnosis of asthma in the British population (odds ratio 2.35, p<0.01), but not in the Japanese population. Multiple logistic regression analysis also showed that CCR3 T51C was associated with asthma (odds ratio 2.83, p < 0.02), independent of atopic phenotypes such as high levels of total or house dust mite-specific immunoglobulin-E in serum. In conclusion, a significant association between asthma and CCR3 T51C polymorphism localized on chromosome 3p21 was found.
European Respiratory Journal 01/2001; 17(1):59-63. · 5.89 Impact Factor
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M Nakamura,
S Fujishima,
M Sawafuji,
A Ishizaka,
T Oguma,
K Soejima,
H Matsubara,
S Tasaka,
K Kikuchi,
K Kobayashi,
E Ikeda,
M Sadick,
C A Hebert,
N Aikawa, M Kanazawa,
K Yamaguchi
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ABSTRACT: Reexpansion of a collapsed lung induces increased microvascular permeability leading to reexpansion pulmonary edema (REPE). This study was designed to prove the hypothesis that local overproduction of interleukin-8 (IL-8) induces inflammatory cell accumulation which leads to the induction of REPE. Initially, we examined the detailed characteristics of a rabbit model of REPE in association with IL-8 production and its mRNA expression. The lung tissue to plasma ratio of radiolabeled albumin (T/P ratio), the lung wet to dry ratio, and bronchoalveolar lavage (BAL) neutrophil counts were significantly increased in the reexpanded lung. IL-8 concentrations and mRNA expression were significantly increased in the reexpanded lung homogenate. Immunohistochemically, alveolar macrophages (AMs) and epithelial cells in the reexpanded lung and AMs in the collapsed lung were positive for IL-8. Second, we examined the effect of pretreatment with a specific monoclonal anti-IL-8 antibody (Ab) or control IgG on the development of REPE. The T/P ratio and BAL neutrophil counts were conspicuously decreased by pretreatment with anti-IL-8 Ab, but not with control IgG. On a histopathological study, lung injury and leukocyte infiltration were attenuated by the pretreatment with anti-IL-8 Ab. In conclusion, IL-8 production is enhanced in the reexpanded lung, and contributes to the development of REPE. The pretreatment with anti-IL-8 antibody may be useful as a novel protective therapy for this disease.
American Journal of Respiratory and Critical Care Medicine 04/2000; 161(3 Pt 1):1030-6. · 11.08 Impact Factor
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H Nakamura,
S Fujishima,
T Inoue,
Y Ohkubo,
K Soejima,
Y Waki,
M Mori,
T Urano,
F Sakamaki,
S Tasaka,
A Ishizaka, M Kanazawa,
K Yamaguchi
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ABSTRACT: The clinical and immunoregulatory effects of long-term macrolide antibiotic therapy for patients with chronic lower respiratory tract infections (CLRTI) were investigated. Clinical parameters and neutrophil chemotactic mediators in the epithelial lining fluid (ELF) of CLRTI patients (n = 10) were examined before and after 3 months oral administration of roxithromycin (RXM). The in vitro effects of RXM were also examined on the release of these mediators from alveolar macrophages (AM) and neutrophils. Arterial oxygen tension (p<0.05), vital capacity (VC) (p<0.001), %VC (p<0.05) and forced expiratory volume in one second (p<0.01) were improved after RXM treatment, but airway bacteria were not eradicated. Among the mediators, the levels of interleukin (IL)-8, neutrophil elastase (NE) and leukotriene B4 (LTB4) were higher in ELF than in plasma of CLRTI patients and they decreased after RXM treatment (n = 7, p<0.05 for each). RXM concentrations were significantly increased in the bronchoalveolar lavage cells of the treated patients. In in vitro experiments, RXM showed inhibitory effects on IL-8 release from AM and neutrophils. In conclusion, interleukin-8, neutrophil elastase and leukotriene B4 contribute to the neutrophilic inflammation in the airways of chronic lower respiratory tract infection patients and the clinical effects of roxithromycin may, in part, be attributable to the suppression of excess release of the chemotactic mediators from inflammatory cells.
European Respiratory Journal 07/1999; 13(6):1371-9. · 5.89 Impact Factor
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ABSTRACT: Platelet-activating factor (PAF), a phospholipid with a wide range of proinflammatory actions, is immediately degraded and inactivated in vivo by PAF acetylhydrolase (PAF-AH). Surprisingly, 4% of the Japanese population lacks the extracellular isoform of this enzyme, plasma PAF-AH, due to a genetic missense (V279F) mutation. We studied the association of this mutation with asthma prevalence and phenotypes in the Japanese adult population. The allele frequency of V279F mutation was 18.6% in 279 patients with asthma (28.7% heterozygotes and 4.3% homozygotes) and 21.7% in 217 healthy subjects (32.3% heterozygotes and 5.5% homozygotes). V279F mutant allele prevalence was consistent regardless of asthma type (16.3% in atopic [n = 156] and 21.6% in nonatopic [n = 123]), or the severity of disease (21.7% in patients with mild [n = 97], 17.5% in those with moderate [n = 131], and 15.8% in those with severe [n = 51] asthma). Plasma PAF-AH activity was inversely proportional to the number of mutant alleles, and did not correlate with asthma prevalence, type, or severity. We concluded that plasma PAF-AH deficiency due to V279F mutation is not essential to the pathophysiology of asthma in the Japanese adult population.
American Journal of Respiratory and Critical Care Medicine 04/1999; 159(3):974-9. · 11.08 Impact Factor
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ABSTRACT: A 60-year-old man was admitted to our hospital complaining of non-productive cough. He had worked in Africa and received a blood transfusion after a traffic accident in 1985. On admission, the patient had remarkable hypoxemia and a decreased CD4+ lymphocyte count. A serological test for human immuno-deficiency virus (HIV)-1 was positive. His chest radiographs showed diffuse reticular and linear opacities, and broncoalveolar lavage findings established a diagnosis of Pneumocystis carinii pneumonia (PCP). A high-resolution CT of the chest revealed peripheral infiltrates and low attenuation areas (LAA) consistent with severe emphysematous alterations. We administered high-dose methylprednisolone and trimethoprim-sulphamethoxazole (TMP-SMX). Because of marked eosinophilia, TMP-SMX was discontinued, and the patient was given inhaled pentamidine isothiocyanate. Although there was a striking clinical improvement, the emphysema-like lesion on chest CT remained unaltered. LAA on CT had been modest in 1994, but had markedly enlarged during the three years thereafter, leading us to speculate that most of the LAA lesions recognized on admission might have developed in association with PCP. Pulmonary function tests showed an obstructive ventilatory defect and impaired diffusing capacity. Although PCP classically presents with diffuse ground-glass or fine granular opacities, thin-walled cavities or other atypical findings have recently been reported, especially in AIDS patients. There have been several reports about emphysema-like lesions associated with PCP. It was suggested that these lesions might be due to lung parenchyma destruction induced by HIV itself or increased elastase release from HIV-infected macrophages. This is the first report of PCP with pulmonary emphysematous lesions in Japan.
Nihon Kokyūki Gakkai zasshi = the journal of the Japanese Respiratory Society. 04/1998; 36(3):283-7.
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ABSTRACT: A 65-year-old man with rapidly progressing small cell lung cancer found in the course of renal failure is reported. The patient had a medical history of hypertension, diabetes mellitus, and cardiovascular disease. Hemodialysis was introduced following renal failure, but pneumonia resulted in a transient exacerbation and his complaint of general fatigue did not improve. Examination for the fatigue revealed no apparent abnormalities. Three months later, he died of small cell lung cancer.
The Keio Journal of Medicine 04/1998; 47(1):45-51.
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ABSTRACT: A 55-year-old woman was admitted to our hospital with progressive dyspnea that had begun one month before. Chest rentogenogram revealed groundglass appearance and reticular shadows bilaterally. Pulmonary function tests showed both decreased vital capacity and diffusing capacity. Bronchoalveolar lavage fluid had a high lymphocyte fraction with a low CD4+/CD8+ ratio. Thoracoscopic lung biopsy revealed thick, fibro-edematous interstitium and diffuse infiltration of lymphocytes. We also observed an intra-alveolar exudate with infiltration of histiocytes and lymphocytes. The clinical features and pathological findings were consistent with subacute interstitial pneumonia, which was the entity proposed by Kawabata and colleagues. The patient developed acute respiratory failure four days after lung biopsy and died despite steroid pulse therapy. Although subacute interstitial pneumonia has been reported to respond to steroid therapy, and to have a good prognosis, we believe that subacute interstitial pneumonia could fatally worsen when associated with lung biopsy, infection, or some other stimulus.
Nihon Kokyūki Gakkai zasshi = the journal of the Japanese Respiratory Society. 03/1998; 36(2):182-6.
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ABSTRACT: A 61-year-old man with superficial bladder cancer, which was detected after he complained of hematuria, was treated three times with intravesical BCG administration. Since liver dysfunction was detected thereafter, he was admitted to our hospital. Three days after admission, he complained of dyspnea on exertion associated with severe hypoxemia, as well as abnormal findings on chest X-ray, i.e. extensive bilateral lung densities. We performed bronchoscopic examination and obtained bronchoalveolar lavage fluid (BALF) and lung biopsy specimens (TBLB). In the BALF, a marked increase in the total cell number, particularly lymphocytes with a high CD4/CD8 ratio was noted. TBLB specimens revealed the lesions to be numerous non-caseating granulomas. We failed to obtain definite evidence of BCG in the sputum, urine, blood, and BALF. Instead, we found that a lymphocyte stimulation test for BCG (DLST) was strongly positive. Based on these findings, severe interstitial pneumonia probably induced by hypersensitivity against BCG, was diagnosed. Anti-tuberculous agents, and steroid-pulse therapy followed by oral administration of relatively low dose of steroid ameliorated the abnormal conditions, including chest X-ray film findings and hypoxemia. The population of lymphocytes and CD4/CD8 ratio in the BALF were reduced as well. Serious interstitial pneumonia was induced by the intravesical administration of BCG, which resulted in transitional changes in the BALF cell component.
Nihon Kyōbu Shikkan Gakkai zasshi 01/1998; 35(12):1383-8.
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ABSTRACT: Preembedding immunogold electron microscopy was performed to evaluate the position of outer arm dynein heavy chains in normal human respiratory cilia. Anti-dynein antibody (AD2), which is specific for sea urchin sperm flagellar dynein heavy chains, was used as primary antibody. Direct cross-sections of cilia were selected, and the distance between the center of a cilium and the center of a colloidal gold particle attached to the cilium (X) was measured. The distance between the center of a cilium and the farthest edge of an outer dynein arm of the cilium was measured by ordinary electron microscopy (Yo) and by immunoelectron microscopy (Yi). X was significantly longer than Yo and Yi. If it is assumed that the structure of respiratory cilia is dense and that antibodies are located at the outer side of the actual position of the heavy chains, then the average distance difference of approximately 90-120 A may represent the length of two conjugated antibodies. This length should be kept in mind when performing immunoelectron microscopy. The data suggest that AD2 recognizes the outer arm dynein heavy chains of normal human respiratory cilia.
Microscopy Research and Technique 10/1997; 38(5):500-4. · 1.79 Impact Factor
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ABSTRACT: We examined the expression of interleukin (IL)-8 receptors (Rs), type A (IL-8-RA) and type B (IL-8-RB), on peripheral blood and bronchoalveolar lavage (BAL) fluid neutrophils; we also examined IL-8 and other chemoattractants in the epithelial lining fluid (ELF) of patients with chronic lower respiratory tract infection (CLI) to elucidate the in vivo regulation of IL-8Rs. Neutrophils were stained with monoclonal antibodies specific for IL-8-RA and IL-8-RB. We detected higher levels of IL-8 (81.6 +/- 25.4 ng/ml, mean +/- SE), leukotriene (LT) B4, and IL-1 beta in the ELF of the CLI patients than in their serum (P < 0.05). The expression of IL-8Rs on BAL neutrophils was significantly lower than that on peripheral blood neutrophils (P < 0.01 for both). In vitro analysis showed that low-level IL-8 (50 ng/ml) alone did not affect IL-8R expression but that it was downregulated by high-level IL-8 (500 ng/ml) alone and by low-level IL-8 in combination with LTB4 or IL-1 beta. Staurosporine reduced the downmodulation by low-level IL-8 plus LTB4 or IL-1 beta but not by high-level IL-8 alone. We speculate that pulmonary IL-8-RA and IL-8-RB may have been downmodulated by the combined effect of local chemoattractants through, in part, a protein kinase C-dependent mechanism.
The American journal of physiology 09/1997; 273(3 Pt 1):L618-25.
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ABSTRACT: A 68-year-old man, who had continuing exposure to budgerigars, developed fatal acute respiratory failure following years of slowly progressive pulmonary deterioration. His lung function was characterized first by mild airflow obstruction and later by progressive loss of lung volume. Computed tomography showed progressive development of pulmonary fibrosis and honeycombing. His serum disclosed precipitins to pigeon antigen. During his final illness his chest radiograph showed widespread patchy consolidation. At autopsy, his lungs revealed left lower lobe bronchopneumonia, fibrosis and honeycombing at the bases and widespread evidence of diffuse alveolar damage with organized exudate in some alveoli. To our knowledge, this is the second reported fatality due to acute alveolar injury in bird fanciers' lung.
Respiration 02/1997; 64(4):307-9. · 2.26 Impact Factor
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ABSTRACT: The clinical features of pulmonary tuberculosis associated with acquired immunodeficiency syndrome (AIDS) in Japan were surveyed utilizing questionnaires completed by 48 institutes around the Tokyo metropolitan area. We found 11 Japanese and six foreign patients. The average number of patients per institute was 0.37. The Japanese patients had advanced human immunodeficiency virus (HIV) infection. A middle aged man, with fever and cough, nonspecific chest X-ray infiltrates, decreased lymphocyte counts, and a negative tuberculin skin test was the typical presentation of the Japanese patients. The clinical diagnosis was often difficult. The smear positive rate was high among those from whom smears were obtained, suggesting high communicability. None of the isolates indicated multidrug-resistant tuberculosis at the time of diagnosis. In conclusion, sputum smear and culture remain the keys to diagnosing tuberculosis in patients with AIDS, although the clinical picture may be atypical for pulmonary tuberculosis.
Internal Medicine 01/1997; 35(12):946-52. · 0.94 Impact Factor
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S Tasaka,
A Ishizaka,
T Urano,
K Sayama,
F Sakamaki,
H Nakamura,
T Terashima,
Y Waki,
K Soejima,
M Nakamura,
H Matsubara,
S Fujishima, M Kanazawa,
J W Larrick
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ABSTRACT: Cationic antimicrobial protein of 18 kD (CAP18) was identified and purified from rabbit granulocytes and shown to inhibit various activities of lipopolysaccharide (LPS). We investigated the effect of a 32-amino-acid C-terminal fragment of CAP18 (CAP18-derived peptide, CDP) on the pathogenesis of acute lung injury caused by intravenous endotoxin. Guinea pigs were divided into six groups: (I) saline control (n = 8), (2) CDP-alone (n = 8), (3) LPS-alone (n = 8), (4) LPS+CDP0m (n = 8), (5) LPS+CDP10m (n = 8), and (6) LPS+CDP60m (n = 8). A CDP dose of 0.2 mg/kg was injected at various time points after LPS injection. Lung wet-to-dry weight ratio, [125I]albumin leakage in lung tissue and bronchoalveolar lavage (BAL) fluid, differential cell count in BAL fluid, and histopathologic features were examined 4 h after intravenous administration of 0.02 mg/kg of LPS. The LPS+CDP0m and the LPS+CDP10m groups showed significantly attenuated lung injury compared to that seen in the LPS-alone group, however the LPS+CDP60m group revealed no attenuation of lung injury. The accumulation of peripheral white blood cells into pulmonary vasculature was attenuated only in the LPS+CDP0m but not in the LPS+CDP10m groups. We examined the effect of CDP on the expression of adhesion molecules using human umbilical vein endothelial cells, the result of which showed that CDP suppressed the LPS-induced expression of adhesion molecules in a dose-dependent manner. We conclude that CDP attenuates inflammatory cell migration into alveoli resulting in the attenuation of lung injury.
American Journal of Respiratory Cell and Molecular Biology 01/1997; 15(6):738-44. · 5.13 Impact Factor
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ABSTRACT: We studied the role of adhesion molecules in acute lung injury caused by lipopolysaccharide (LPS). Forty-eight female guinea pigs were divided into three groups: saline (n = 12); B464, an LPS antagonist, (0.2 mg/kg i.v.) (n = 12); LPS (0.02 mg/kg i.v.) (n = 12); and LPS + B464 (n = 12). The numbers of polymorphonuclear cells (PMN) in blood sampled over 4 hours were counted. Accumulation of PMNs in the lungs was determined by counting the number of PMNs in lung-tissue samples fixed for light-microscopic examination. The lung wet-to-dry weight ratio and the 125I-albumin tissue-to-plasma ratio were used to assess lung injury. Human umbilical-vein endothelial cells were treated with B464 and then stimulated with either LPS or tumor necrosis factor. Expression of ICAM-1 and ELAM-1 was estimated by enzyme-linked immunosorbent assay. After LPS injection, light microscopy revealed decreases in peripheral PMN counts, and accumulation of PMNs in the lungs. Increases in the two indices of lung injury were also observed. These changes were attenuated by prior treatment with B464. The LPS-induced increases in ICAM-1 and ELAM-1 expression were dose-dependently suppressed by B464. These results suggest that pulmonary accumulation of activated PMNs plays an important role in LPS-induced lung injury.
Nihon Kyōbu Shikkan Gakkai zasshi 01/1997; 34 Suppl:136-40.
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K Soejima,
A Ishizaka,
T Urano,
K Sayama,
F Sakamaki,
H Nakamura,
T Terashima,
Y Waki,
S Tasaka,
S Fujishima,
T Kawata,
W J Christ, M Kanazawa
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ABSTRACT: B464 is a novel synthetic analog of lipid A, a toxic component of endotoxin (LPS; lipopolysaccharide). We investigated the effects of B464 on both LPS-induced cellular responses in vitro and acute lung injury in vivo. In the in vitro study, B464 inhibited tumor necrosis factor-alpha (TNF-alpha) production from human monocytes, priming and stiffening of neutrophils, and expression of adhesion molecules on endothelial cells induced by LPS. We then studied the effects of B464 pretreatment on acute lung injury elicited by intravenous LPS administration in vivo. Guinea pigs were divided into saline control, B464 alone, LPS alone, and LPS + B464 groups. Animals were observed for 4 h after LPS administration, and lung injury was evaluated by extravascular lung water, 125I-albumin leakage in lung tissue, and lung neutrophil accumulation. In the LPS alone group, rapid and sustained peripheral neutropenia (p < 0.001 versus saline at 15 min and at 1, 2, and 4 h), an increased plasma TNF-alpha concentration (p < 0.005 at 1 h), and increases in lung injury parameters (p < 0.05) were observed. In the LPS + B464 group, no changes were observed in either plasma TNF-alpha or lung injury parameters. Transient peripheral neutropenia and subsequent rapid recovery (p > 0.05, p < 0.001, p < 0.01, and p > 0.05 at 15 min and 1, 2, and 4 h, respectively) were observed in the LPS + B464 group. These in vivo data, together with in vitro evidence of suppressed cellular responses, suggest that B464 (1) inhibits neutrophil accumulation in lung tissue, and (2) attenuates the development of acute lung injury by blocking the activation of neutrophils and mononuclear cells as well as the interaction between neutrophils and endothelial cells.
American Journal of Respiratory and Critical Care Medicine 11/1996; 154(4 Pt 1):900-6. · 11.08 Impact Factor
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ABSTRACT: We studied blood MIP-1 alpha and IL-8 in 38 septic patients and 5 healthy volunteers. Both chemokines were undetectable in the healthy volunteers. In sepsis, serum MIP-1 alpha was detected in 45% of the patients and Il-8 in 84%. The levels of MIP-1 alpha, but not of IL-8, correlated with CRP, IL-6 and TNF alpha levels. Complications, including various organ failures and mortality, showed no correlation with serum MIP-1 alpha levels. In contrast, we found increased levels of serum IL-8 in septic patients with disseminated intravascular coagulation, central nervous system (CNS) dysfunction or renal failure, and the mortality rate was higher in the IL-8 detectable group than in the IL-8 undetectable group (50% vs 0%, p < 0.05). In conclusion, the production of both MIP-1 alpha and IL-8 was increased and initially detectable levels of circulating IL-8 predicted high mortality in sepsis.
To determine the significance of the C-C chemokine MIP-1 alpha and the C-X-C chemokine IL-8 in sepsis.
Prospective study.
Clinical investigation, emergency department and general intensive care unit of university hospital.
38 septic patients and 5 healthy volunteers were studied. Sepsis was diagnosed following the criteria formulated by ACCP/SCCM.
10-20 ml of blood was drawn from each patient at the time of initial diagnosis of sepsis.
MIP-1 alpha and IL-8 were determined by sandwich ELISA. Both chemokines were undetectable in the healthy volunteers. In sepsis, serum MIP-1 alpha was detected in 45% of the patients and IL-8 was detected in 84%. The levels of MIP-1 alpha, but not of IL-8, correlated with CRP, IL-6 and TNF alpha levels. Complications, including various organ failures and mortality, showed no correlation with serum MIP-1 alpha levels. In contrast, we found increased levels of serum IL-8 in patients with disseminated intravascular coagulation (DIC) (p < 0.05), central nervous system (CNS) dysfunction (p < 0.05), renal failure (p < 0.01) and the mortality rates were higher in the IL-8 detectable group than in the IL-8 undetectable group (50% vs 0%, p < 0.05).
The production of MIP-1 alpha and IL-8 was increased in sepsis. Furthermore, an initially detectable level of circulating IL-8, but not MIP-1 alpha, predicted a high mortality in sepsis diagnosed according to the ACCP/SCCM criteria.
Intensive Care Medicine 11/1996; 22(11):1169-75. · 5.40 Impact Factor
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M Kanazawa
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ABSTRACT: Acute lung injury (ALI) was defined recently as a syndrome of inflammation and increased permeability of the lungs that is associated with clinical radiologic, and physiologic abnormalities that can not be explained by left atrial hypertension. ALI has the same clinical spectrum, although in a milder form, as acute respiratory distress syndrome (ARDS). The risk factors, incidence, and prognosis of ALI are described based on the medical literature and data collected at Keio University Hospital. We estimate that 20,000 to 40,000 cases of ALI, half of which also have ARDS, occur annually in Japan. Despite the new diagnostic criteria, the clinical entity of ALI remains to be clarified both physiologically and biochemically because of the lack of direct diagnostic methods. I briefly review the central mediator(s) and their role in the inflammatory cascade of ALI. Experimental studies and pharmacological interventions from our laboratory are also described.
The Keio Journal of Medicine 10/1996; 45(3):131-9.
