Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P10145 (IL-8)
 23,849 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The use of OKT3 as an immunosuppressive agent is accompanied by increased cytokine production and constellation of side effects collectively termed cytokine release syndrome (CRS). Pentoxifylline (PTF) inhibits synthesis of some cytokines, and has been shown to attenuate CRS when administered before OKT3. In this double-blinded, placebo-controlled study, 46 renal allograft recipients were randomized to receive either PTF (800 mg q 8 hr for at least 24 h) p.o. or placebo, along with methylprednisolone (7 mg/kg), diphenhydramine, and acetaminophen, prior to beginning OKT3 as therapy for acute rejection. Patients were observed, and symptoms scored semiquantitatively. Despite the presence of therapeutic PTF levels (721 +/- 726 ng/ml), the frequency and severity of side effects (fever, chills, headache, neurocortical symptoms, dyspnea, nausea, vomiting, diarrhea) did not differ between treatment groups. Likewise PTF did not affect renal function or immunologic response to OKT3, with similar graft and patient survival in both groups. Plasma levels of TNF alpha, IFN gamma, IL-6, and IL-8 increased as predicted following OKT3 administration, without significant differences between PTF and placebo groups. In this controlled, multicenter trial, pretreatment with oral PTF was ineffective in attenuating OKT3-related CRS in renal allograft recipients.
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PMID:Pentoxifylline does not prevent the cytokine-induced first dose reaction following OKT3--a randomized, double-blind placebo-controlled study. 861 Mar 83

CM101 is a bacterial polysaccharide that induces neovascular inflammation in malignant tumors. Fifteen patients with refractory malignancies received CM101 i.v. by a 15-min infusion every other day, three times in 1 week, at doses ranging from 1 unit (7.5 microgram)/kg to 5 units/kg. Serum was analyzed for anti-CM101 IgG and IgM weekly. Plasma levels of inflammatory cytokines, including tumor necrosis factor alpha, interleukin 8, interleukin 10, MIP-1alpha, and soluble E-selectin, were analyzed from -15 min to 12 h during each treatment. Dose-limiting toxicities, including grade IV dyspnea and arrhythmia, were encountered at the 5-unit/kg level. Toxicities occurred primarily within the first 12 h after therapy and included mild-to-moderate fever and chills, nausea, cough, headache, facial flushing, dyspnea, myalgias, and acute tumor-related pain. No patient developed detectable antibodies to CM101. All patients experienced marked time- and dose-dependent elevations in all cytokines studied. Three patients experienced tumor shrinkage. The results show that CM101 can be safely administered at doses that produce evidence for severe, and possibly tumor-specific, inflammation. Further study is necessary to better characterize the mechanism of action and determine the optimal dose and schedule of this new agent.
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PMID:Phase I study of the antineovascularization drug CM101. 981 93

Exposure to airborne endotoxin in infancy may protect against asthma by promoting enhanced T(H)1 response and tolerance to allergens. On the other hand, later in life, it adversely affects patients with asthma. Endotoxin binding to receptors on macrophages and other cells generates IL-12, which inhibits IgE responses. It also generates cytokines like IL-1, TNF-alpha, and IL-8, which cause inflammation. These signal transduction pathways resemble those leading to the generation of cytokines, such as IL-4, IL-13, and IL-5, which are responsible for the inflammation of IgE-mediated allergic disease. The main difference seems to be that endotoxin recruits neutrophils, but IgE recruits eosinophils, and the details of the tissue injury from these granulocytes differ. Sources of airborne endotoxin include many agricultural dusts, aerosols from contaminated water in many industrial plants, contaminated heating and air-conditioning systems, mist-generating humidifiers, and damp or water-damaged homes. Acute inhalation of high concentrations of endotoxin can cause fever, cough, and dyspnea. Chronic inhalation of lesser amounts causes chronic bronchitis and emphysema and is associated with airway hyperresponsiveness. Airborne endotoxin adversely affects patients with asthma in 3 ways: (1) by increasing the severity of the airway inflammation; (2) by increasing the susceptibility to rhinovirus-induced colds; and (3) by causing chronic bronchitis and emphysema with development of irreversible airway obstruction after chronic exposure of adults. The most effective management is mitigating exposure. The potential of drug treatments requires further clinical investigation.
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PMID:Endotoxin-stimulated innate immunity: A contributing factor for asthma. 1149 29

Acute exacerbations (AE) represent one of the hallmarks of Chronic Obstructive Pulmonary Disease (COPD). They are characterised by increased from baseline dyspnoea, cough and sputum production and/or purulence, variably associated with fever and systemic symptoms. As in stable COPD, airway inflammation is an important part of the disease underlying the clinical manifestations. Studies on airway inflammation in AE by means of invasive methodologies (e.g. fiberoptic bronchoscopy with bronchial biopsy and/or bronchoalveolar lavage) are difficult due to clinical, practical and ethical issues. New and less- (sputum) or non-invasive methodologies (exhaled markers) are becoming increasingly applied also to the study of AE in COPD. The overall data on airway inflammation during AE seems to indicate an "acute on chronic" picture of inflammation, with increased proportions of inflammatory cells in tissue and lavage/sputum samples and with the change in the proportions of some of the cell types, such as a substantial increase in the numbers of eosinophils. Cytokines and inflammatory mediators involved in AE seem to be those related to PMN chemotaxis (IL-8 and LT) and those related to eosinophilic inflammation. A more precise categorisation of the event causing AE (e.g. viral vs. bacterial), and of the baseline patients' characteristics (e.g. severe vs. mild-moderate stage) associated with a wider application of well-standardised non-invasive methodologies could bring us in the future better clues on the pattern of airway inflammation during AE.
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PMID:Acute exacerbations of COPD: is inflammation central to prevention and treatment strategies? 1281 45

Chronic obstructive pulmonary disease is a major health problem with cigarette smoking as its major risk factor. Current therapies are directed against the symptoms (e.g., breathlessness and mucus production) or the chronic airway inflammation. However, the excessive annual decline in lung function and the airway inflammation have not yet been shown to be improved by these strategies. New potential drug therapies are directed against specific components of the inflammation. Novel drugs have been developed for treatment of inflammatory diseases including chronic obstructive pulmonary disease in order to antagonise cytokines and chemokines such as TNF-alpha, CXC chemokine ligand 8 (IL-8) or CC chemokine ligand 2 (monocyte chemoattractant protein 1) that orchestrate the inflammatory process. Some of these drugs are shown to be effective in patients with other chronic inflammatory diseases but still have to prove their efficacy in the treatment of chronic obstructive pulmonary disease.
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PMID:Potential new drugs for therapy of chronic obstructive pulmonary disease. 1283 44

This study examined inflammatory responses from primary cultured human bronchial epithelial cells in chronic obstructive pulmonary disease (COPD) and the clinical factors modulating them. Epithelial cells from bronchoscopic biopsies from 14 patients with COPD ((mean +/- SD) age 74.6 +/- 5.7 yrs, forced expiratory volume in one second (FEV1) 1.21 +/- 0.36 L, FEV1 %, predicted 51.1 +/- 15.8%, 51.5 +/- 24.0 pack-yrs of smoking, inhaled steroid dosage 1237.5 +/- 671.0 microg x day(-1), Medical Research Council (MRC) dyspnoea score 3.18 +/- 1.33) and eight current/exsmokers with normal pulmonary function (age 60.4 +/- 13.5 yrs, FEV1 2.66 +/- 1.27 L, FEV1 % pred 89.6 +/- 17.7%, 49 +/- 44 pack-yrs of smoking, MRC dyspnoea score 1 +/- 0) were grown in primary culture and exposed to 50 ng x mL(-1) tumour necrosis factor-alpha. Stimulated COPD cells produced significantly more interleukin (IL)-6 at 24 and 48 h, and IL-8 at 6 and 24 h than unstimulated COPD cells. This response was not seen in cells from current/exsmokers. IL-6 and IL-8 production was lower in COPD patients taking inhaled steroids. Following an inflammatory stimulus, bronchial epithelial cells in chronic obstructive pulmonary disease show a significant cytokine response not seen in smokers with normal pulmonary function and this may be modified by inhaled steroid therapy.
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PMID:Airway epithelial inflammatory responses and clinical parameters in COPD. 1288 57

We report a rare case of a cute lymphoblasticleukemia (ALL) who developed dyspnea, neurological disturbance with illusions, pancytopenia, phagocytosis and coagulation disturbances following bacterial tonsillitis. The values of soluble interleukin-2 receptor (sIL-2R), IL-6 and IL-8 were also elevated. Her clinicolaboratory findings were similar to hemophagocytic lymphohistiocytosis (HLH), which is a cytokine disease induced by activated T cells and macrophages. Atypical HLH following bacterial tonsillitis should be kept in mind in leukemia patients.
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PMID:Atypical hemophagocytic lymphohistiocytosis following bacterial tonsillitis in acute lymphoblastic leukemia. 1291 81

A 30-year-old woman who had been receiving minocycline for 11 days to treat a skin burn presented with high fever and progressive dyspnea. Chest radiography demonstrated bilateral pulmonary infiltrates with ground glass opacities. She was admitted to our hospital under a tentative diagnosis of minocycline-induced pneumonia. Minocycline therapy was discontinued at hospital admission, which led to dramatic clinical and radiographic improvement. Bronchoalveolar lavage fluid (BALF) analysis three days after the onset of the pneumonia showed increased numbers of total cells (7.68 x 10(5)/ml), neutrophils (33%) and eosinophils (14%). An increased number of peripheral blood neutrophils was also noted at the time of hospital admission. Follow-up evaluations of BALF 10 days and 34 days after the onset showed rapidly declining numbers of neutrophils and eosinophils. We also measured the levels of several cytokines in BALF, suggesting that TNF-alpha and IL-8 contributed to the accumulation of neutrophils, whereas IL-5 contributed to the accumulation of eosinophils. In summary, we report here the temporal change in the inflammatory cell and cytokine profile in BALF, serum, or both, in a case of drug-induced pneumonia.
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PMID:[Case of drug-induced pneumonia followed by sequential bronchoalveolar lavage]. 1545 48

Drug reactions can be considered as being either predictable or unpredictable. A predictable reaction would be the result of the pharmacologic action of the medication. An unpredictable reaction might be idiosyncratic, might be drug intolerance, or might have or imply an immunologic basis, such as being IgE mediated. Immediate reactions that are not IgE mediated can be considered as pseudoallergic (non-IgE-mediated mast cell activation). This review will discuss allergic and immunologic reactions to immunomodulators, penicillins and cephalosporins, sulfonamides, aspirin, and nonselective nonsteroidal anti-inflammatory drugs and consider the serious drug-related conditions of Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). The field of drug "allergy" has expanded to include adverse reactions associated with immunosuppressive medications, anticytokine therapies, and mAbs. The cytokine release reaction that occurs with anti-CD20 antibody infusions in patients with leukemia and white blood cell counts of greater than 50 x 10(9)/L is associated with high concentrations of TNF, IL-6, and IL-8. Because of the findings of fever, dyspnea, rigors, and hypotension, this reaction resembles the Jarisch-Herxheimer reaction that occurs 60 to 90 minutes after penicillin administration in patients with secondary syphilis. Furthermore, the care of the patient with penicillin allergy has been made more difficult in the absence of the major determinant, penicilloyl-polylysine, in that from 34% to 84% of patients who have positive skin test reactions to penicillin have exclusively positive reactions to the major determinant. SJS and TEN typically are caused by medications within 1 to 8 weeks of initiation of therapy. Evidence for death of the keratinocytes through (1) drug-specific cytotoxicity with the perforin-granzyme B-mediated killing and (2) activation of Fas on keratinocytes have provided explanations for the sloughing of skin. Unfortunately, intravenous immunoglobulin therapy for SJS and TEN has been disappointing.
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PMID:8. Drug allergy. 1645 48

Severe acute respiratory syndrome (SARS) is a recently emerged infectious disease with significant morbidity and mortality. An epidemic in 2003 affected 8,098 patients in 29 countries with 774 deaths. The aetiological agent is a new coronavirus spread by droplet transmission. Clinical and general laboratory manifestations included fever, chills, rigor, myalgia, malaise, diarrhoea, cough, dyspnoea, pneumonia, lymphopenia, neutrophilia, thrombocytopenia, and elevated serum lactate dehydrogenase (LD), alanine aminotransferase (ALT) and creatine kinase (CK) activities. Treatment has been empirical; initial potent antibiotic cover, followed by simultaneous ribavirin and corticosteroids, with or without pulse high-dose methylprednisolone, have been used. The postulated disease progression comprises (1) active viral infection, (2) hyperactive immune response, and (3) recovery or pulmonary destruction and death. We investigated serum LD isoenzymes and blood lymphocyte subsets of SARS patients, and found LD1 activity as the best biochemical prognostic indicator for death, while CD3+, CD4+, CD8+ and natural killer cell counts were promising predictors for intensive care unit (ICU) admission. Plasma cytokine and chemokine profiles showed markedly elevated Th1 cytokine interferon (IFN)-gamma, inflammatory cytokines interleukin (IL)-1beta, IL-6 and IL-12, neutrophil chemokine IL-8, monocyte chemoattractant protein-1 (MCP-1), and Th1 chemokine IFN-gamma-inducible protein-10 (IP-10) for at least two weeks after disease onset, but there was no significant elevation of inflammatory cytokine tumor necrosis factor (TNF)-alpha and anti-inflammatory cytokine IL-10. Corticosteroid reduced IL-8, MCP-1 and IP-10 concentrations from 5-8 days after treatment. Measurement of biochemical markers of bone metabolism demonstrated significant but transient increase in bone resorption from Day 28-44 after onset of fever, when pulse steroid was most frequently given. With tapering down of steroid therapy, there was a decrease in bone resorption marker together with an increase in bone formation markers round Day 50, suggesting that some of the bone loss might be reversed. Our research studies on the chemical pathology and clinical immunology of SARS should have implications for the pathophysiology and therapy of this potentially lethal infection.
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PMID:Severe acute respiratory syndrome: clinical and laboratory manifestations. 1845 12


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