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Query: UMLS:C0018681 (headache)
 56,091 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Infection-induced malnutrition, the most common form of cytokine-induced malnutrition, results from the actions of proinflammatory cytokines, ie, tumor necrosis factor (TNF) and interleukins 1,6, and 8 (IL-1, IL-6, and IL-8). During acute generalized infections, these cytokines initiate the acute-phase reaction. This reaction is quite stereotyped, and includes fever, malaise, myalgia, headaches, cellular hypermetabolism, and multiple endocrine and enzyme responses. In addition, there is heightened catabolism of muscle proteins and many amino acids; flux of free amino acids into the liver; hepatic synthesis of acute-phase plasma proteins; sequestration of iron and zinc; gluconeo-genesis; insulin resistance; impaired cellular uptake of fatty acids from plasma triglycerides; sizable losses of body nitrogen, potassium, magnesium, phosphate, and zinc; retention of body salt and water; heightened metabolic degradation and/or loss of vitamins; and an activation of the immune system. The pathogenesis of cytokine-induced malnutrition is thus vastly different from the malnutrition caused by uncomplicated starvation. Cytokine-induced malnutrition can have a devastating effect on the immune system and its functions. Although proinflammatory cytokines are found in mucosal fluids, where they contribute to the pathogenesis of inflammatory bowel diseases, it is not known whether cytokines play a role in toxigenic, secretory diarrheas such as cholera, which cause huge losses of body water, electrolytes, and bicarbonate while exhibiting no systemic manifestations of an acute-phase reaction.
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PMID:Herman Award Lecture, 1995: infection-induced malnutrition--from cholera to cytokines. 757 15

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

Cells of the monocyte/macrophage lineage have shown antitumor activity in vitro and in murine models after activation with interferon (IFN) gamma. In vitro data suggest an additional effect on macrophage antitumor activity when IFN gamma is combined with endotoxin (lipopolysaccharides; LPS). In this study we treated nine cancer patients with a total of 62 MAK infusion cycles with autologous macrophages given intravenously (i.v.) after in vitro activation with IFN gamma and LPS. Low-grade fever (WHO I/II) was the commonest side-effect. Chills, nausea, and headache were noted when the number of transfused macrophages exceeded 2 x 10(8). One WHO IV toxicity occurred, consisting of hypotension after transfer of 3 x 10(8) cells, defining this dose as the maximum cell number tolerated. After pretreatment with ibuprofen, however, the maximum cell number could be increased without reaching dose-limiting toxicity. The highest number of cells reinfused was 15 x 10(8). Circulating interleukin(IL)-6 increased in a dose-dependent manner as did IL-1 receptor antagonist (IL-1RA) and IL-8. Tumor response consisted of one case of stable disease (12 weeks) in a patient with formerly progressing colorectal cancer and progressive diseases in eight patients. This study indicates that reinfusion of autologous LPS-activated macrophages upon pretreatment with ibuprofen is feasible and tolerated without major side-effects.
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PMID:Phase I trial of adoptive immunotherapy of cancer patients using monocyte-derived macrophages activated with interferon gamma and lipopolysaccharide. 943 48

Plain paranasal sinus radiographs including occipitofrontal and occipitomental views often show abnormal shadows in patients with allergic rhinitis. For that reason, the relationship between chronic sinusitis and allergy has been discussed for many years. Type I allergy is thought to be involved in the sinusitis which is called allergic sinusitis. However, there is not enough information pertaining to this disorder. In order to determine the clinical feature and the characteristics of paranasal sinus effusion in allergic sinusitis, we investigated the differences between 20 patients with allergic sinusitis and 20 with non-allergic chronic sinusitis used as controls. Clinical symptoms (nasal discharge, nasal obstruction, headache, postnasal discharge) and anterior rhinoscopic findings (nasal discharge, nasal edema), clinical examinations (type of x ray maxillary sinus shadow, bacteriology of nasal discharge), and pathological features of the paranasal sinus effusion were examined and compared in the two kind of sinusitis. Pathological findings of the effusion sampled from 14 patients with allergic sinusitis and 15 with non-allergic sinusitis included the number of eosinophils, activated eosinophils and neutrophils, concentrations of interleukin (IL)-1 beta, IL-4, IL-5, IL-8, and concentrations of leukotriene C4/D4/E4 and prostaglandin E2. The incidence and degree of postnasal discharge as a symptom and a nasal finding were lower in allergic sinusitis patients than in the controls. Microorganisms were detected less frequently in the allergic group. The number of eosinophils, activated eosinophils and neutrophils was higher in the paranasal sinus effusion of the patients with allergic sinusitis. The concentrations (ng/mg of protein) of IL-1 beta and IL-8 showed no difference between the two groups, but IL-4, and IL-5 were more prevalent per mg of protein in the effusion of allergic sinusitis patients. These findings suggest that the clinical features of allergic sinusitis include a low incidence and degree of postnasal discharge and a low rate of detection of bacteria, and that the sinus effusion is characterized by the presence of more eosinophils, activated eosinophils, and IL-5 than in those of chronic sinusitis.
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PMID:[Clinical features and characteristics of paranasal sinus effusion in allergic sinusitis]. 971 Oct 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

Endotoxins, cell-wall fragments of gram-negative bacteria, are found in various work environments and first measurements have been made in general indoor environments. Endotoxins cause an inflammatory response of the respiratory tract. The response is mediated by the proinflammatory cytokines IL-1, IL-6, IL-8, and TNF-alpha and gives rise to general symptoms (fever, headache, malaise), respiratory symptoms (tightness of chest, dry cough), and lung function decrements. In the work environment endotoxins have been identified in all environments which produce similar symptoms. The qualitative results of experimental and epidemiological studies agree well. The related question whether endotoxins are the biologically active component of organic dust cannot yet be answered because of the gap between the concentration of lipopolysaccharides and of endotoxins necessary to induce the same quantitative effect. Different possible explanations are discussed. Endotoxins are also found in the general environment, especially indoors. Their health relevance needs to be assessed in more detail, especially in subjects with bronchial hyperreactivity.
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PMID:[Endotoxins in the workplace and in the environment]. 1023 2

In spite of proven immunoregulatory effects in vitro of recombinant human interferon-gamma (rhIFN-gamma) in trauma, clinical trials remain inconclusive in such patients. To investigate the in vivo effect of rhIFN-gamma perioperatively in surgical patients we did a pilot study in 46 patients termed anergic by negative delayed-type hypersensitivity (DTH) skin test, who were undergoing major surgery (22 women and 24 men). They received 100 micrograms of rhIFN-gamma subcutaneously (treated [T]; n = 24) in a double-blind, placebo- (control [C]; n = 22) controlled manner on preoperative days -7, -5, and -3. Whole-blood cultures were stimulated on days -7, -1, 4, 7, and 10 for 12 h with or without LPS (1 microgram/mL). Mild side effects such as fever, headache, or chills were observed in 7/24 patients. No major complications occurred and no significant effect of rhIFN-gamma on HLA-DR, IL-1, and IL-8 was demonstrated. PGE2, TNF-alpha and IL-6 levels were elevated perioperatively in T. versus C. Neopterin, a metabolite of activated monocytes and macrophages, was significantly activated on days -1 (C: 7.6 +/- 1.2 versus T: 20.5 +/- 2.4 nmol/mL; P < 0.001), day 1 (C: 8.3 +/- 1.4 nmol/mL versus T: 24.9 +/- 2.8 nmol/mL; P < 0.001), and day 4 (C: 9.5 +/- 1.1 nmol/mL versus T: 16.0 +/- 1.8 nmol/mL; P < 0.05). Due to the overall lack of infectious complications during the investigation, no clinical effect was shown for rhIFN-gamma treatment. DTH skin testing failed to detect high-risk individuals in the patient population studied. In conclusion, we demonstrated in our pilot study that pre-operative immunomodulation with rhIFN-gamma in surgical anergic patients did not show severe side effects and modulated in vitro immunoresponse. A larger clinical trial in better-defined high-risk patients may show whether a reduction of infectious complications can be achieved.
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PMID:Perioperative treatment with human recombinant interferon-gamma: a randomized double-blind clinical trial. 1169 68

Fibromyalgia and chronic hepatitis C infection share many clinical features including prominent somatic complaints such as musculoskeletal pain and fatigue. There is a growing body of evidence supporting a link between cytokines and somatic complaints. This review discusses alterations of cytokines in fibromyalgia, including increased serum levels of interleukin (IL)-2, IL-2 receptor, IL-8, IL-1 receptor antagonist; increased IL-1 and IL-6 produced by stimulated peripheral blood mononuclear cell in patients with FM for longer than 2 years; increased gp130, which is a neutrophil cytokine transducing protein; increased soluble IL-6 receptor and soluble IL-1 receptor antagonist only in patients with fibromyalgia who are depressed; and IL-1 beta, IL-6, and TNF-a by reverse transcriptase-polymerase chain reaction in skin biopsies of some patients with fibromyalgia. In addition, this review describes the mechanism by which alterations in cytokines in fibromyalgia and chronic hepatitis C infection can produce hyperalgesia and other neurally mediated symptoms through the presence of cytokine receptors on glial cells and opiate receptors on lymphocytes and the influence of cytokines on the hypothalamus-pituitary-adrenal axis such as IL-1, IL-6, and TNF-a activating and IL-2 and IFN-a down-regulating the HPA axis, respectively. The association between chronic hepatitis C infection and fibromyalgia is discussed, including a description of key cytokine changes in chronic hepatitis C infection. Future studies are encouraged to further characterize these immunologic alterations with potential pathophysiologic and therapeutic implications.
Curr Pain Headache Rep 2003 Oct
PMID:Fibromyalgia, hepatitis C infection, and the cytokine connection. 1294 86

Recently, the YAMIK sinus catheter (YAMIK) has been reported to be a useful therapeutic device in the treatment of sinusitis. The present study was conducted to compare its delivery of either a normal saline (NS) or a betamethasone solution (0.4 mg/ml) into the paranasal sinuses of 25 patients (39 sides) with chronic sinusitis. The following parameters were evaluated: (1) subjective nasal clinical symptoms (nasal discharge, nasal obstruction, postnasal drip and headache), (2) X-ray photographs (ethmoid and maxillary sinuses) and (3) cytokine levels (IL-1beta, IL-8 and TNF-alpha) by enzyme-linked immunosorbent assay. The total nasal symptom scores significantly decreased after the first therapy, and the total X-ray photograph scores significantly decreased after therapy with either NS or the betamethasone solution. In both NS and betamethasone patients, the levels of IL-1beta and IL-8 had significantly decreased by the 3rd and 2nd weeks after therapy, respectively. In contrast, the TNF-alpha level decreased after the first therapy with betamethasone solution and remained unchanged after therapy with NS. These findings suggest that evacuation of the pathological effusions in sinuses may exert a beneficial effect by reducing the levels of IL-1beta and IL-8, and we speculate that removal of pathological effusions from the sinuses may provide treatment through different mechanisms than those that occur in treatment with betamethasone.
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PMID:Cytokine profile in paranasal effusions in patients with chronic sinusitis using the YAMIK sinus catheter with and without betamethasone. 1496 19

Migraine is a common disorder, characterized by recurrent episodes of headache and associated symptoms. The full pathophysiology of migraine is incompletely delineated. Current theories suggest that it is a neurovascular disorder involving cortical depression, neurogenic inflammation and vasodilation. Various neuropeptides and cytokines have been implicated in the pathophysiology of migraine including calcitonin gene-related peptide, interleukin (IL)-1, IL-6 and tumour necrosis factor (TNF)-alpha. There is evidence demonstrating an association between migraine and processes associated with inflammation, atherosclerosis, immunity and insulin sensitivity. Similarly, adiponectin, an adipocytokine secreted by adipose tissue, has protective roles against the development of insulin resistance, dyslipidaemia and atherosclerosis and exhibits anti-inflammatory properties. The anti-inflammatory activities of adiponectin include inhibition of IL-6 and TNF-induced IL-8 formation, as well as induction of the anti-inflammatory cytokines IL-10 and IL-1 receptor antagonist. Adiponectin levels are also inversely correlated with C-reactive protein (CRP), TNF-alpha and IL-6 levels. Likewise, recent studies have shown a possible correlation between CRP, TNF-alpha and IL-6 and migraine attacks. In addition, insulin sensitivity is impaired in migraine and obesity is a risk factor for the transformation from episodic to chronic migraine. In this review we discuss the basic science of adiponectin and its potential connection to the pathophysiology of migraine. Future research may focus on how adiponectin levels are potentially altered during migraine attacks, and how that information can be potentially translated into migraine therapy.
Cephalalgia 2007 May
PMID:Migraine and adiponectin: is there a connection? 1744 81


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