Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0085593 (chills)
 4,268 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Airborne Gram-negative bacteria contamination has been demonstrated in several environments like cotton or flax factories, rooms with humidifiers and sewage treatment plants. Inhalation of LPS by animals provokes a bronchial invasion by neutrophils, a platelet aggregation in pulmonary capillaries, a local immune response and fever. Inhalation by human is related with clinical symptoms like fever, chills, malaise, muscle and joint aches and chest thightness. It appears from data in the literature that LPS airborne contamination is sufficient to provoke such symptoms. It seems important to study more precisely the contamination of suspected air in presence of these symptoms.
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PMID:Effects of bacterial endotoxin inhalation. 728 Mar 43

Therapeutic applications of novel growth factors and cytokines can be limited due to the oftentimes severe inflammatory reactions that are encountered in patients following parenteral administration. These inflammatory responses, hallmarked by fever, headache, and chills are mediated by the release of inflammatory cytokines following administration of protein-based therapeutics. TNF-alpha appears to be one of the most potent and pleiotropic inflammatory cytokines released during the early stages of an inflammatory response. In the present study, we have explored the use of an in vitro assay system to determine whether the release of TNF-alpha from human PBMC could be correlated with documented inflammatory activity in humans. The cytokines tested included rhGM-CSF, rhIL-2, rhIL-3, and rhIFN-gamma, rhG-CSF, which has been shown to lack substantial proinflammatory activity in humans, was also tested. The potent macrophage activator and inflammatory agent, LPS, was used as a positive control. Results of this study demonstrate and confirm an association between the inflammatory activity of cytokines observed in patients and the stimulation of TNF-alpha release from PBMC in vitro. This assay system can be used as a predictive tool in determining the inflammatory potential of novel growth factors and cytokines.
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PMID:TNF-alpha release from human peripheral blood mononuclear cells to predict the proinflammatory activity of cytokines and growth factors. 908 89

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

Amphotericin B is an antifungal drug associated with side effects such as fever and chills, symptoms which may be mediated by pro-inflammatory cytokines such as interleukin-1beta (IL-1beta) and tumour necrosis factor-alpha (TNFalpha). We assessed the capacity of amphotericin B to modulate production of these pro-inflammatory cytokines as well as the anti-inflammatory IL-1 receptor antagonist (IL-1ra), induced by LPS, heat-killed Candida albicans or Staphylococcus aureus. The results of the present study show that amphotericin B slightly increased the production of pro-inflammatory cytokines by human mononuclear cells (PBMC), whereas the production of the anti-inflammatory cytokine IL-1ra was significantly inhibited. This results in a shift towards pro-inflammatory cytokine production, as indicated by a decreased IL-1ra/IL-1beta ratio. Semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR) indicated that levels of IL-1beta and TNFalpha mRNA were increased. In conclusion, amphotericin B is able to cause a shift towards pro-inflammatory cytokine production by human PBMC. This may explain the side effects, such as fever and chills, observed after treatment of patients with amphotericin B.
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PMID:Modulation of the pro- and anti-inflammatory cytokine balance by amphotericin B. 981 45

Intravenous immune gamma-globulin (IVIG) is used successfully in the treatment of Kawasaki disease, with dose-dependent rapid resolution of symptoms such as fever and irritability and a decrease in ESR, WBCs, and platelets. The mode of action of IVIG in reducing this inflammatory response is not clearly understood. Recently anticytokine antibodies in IVIG have been demonstrated. Serum levels of proinflammatory cytokines have been shown to be elevated in patients with Kawasaki disease. The cytokine interleukin-6 (IL-6) is involved in the de novo production of acute-phase proteins by hepatocytes and cause thrombocytosis and fever in response to tissue injury. Patients receiving parenteral recombinant human IL-6 have dose-dependently experienced fever, malaise, chills, and acute-phase reaction. With high IL-6 concentrations, central nervous system toxicity has also been reported and IL-6 has been thought to mediate endothelial damage. We evaluated the response of stimulated blood cells of 12 normal children to IVIG in the release of the cytokines IL-6, IL-8, TNF-alpha. and IL-6 receptor (sIL-6R). The levels of cytokines IL-6, IL-8, and TNF-alpha (but not sIL-6R) in peripheral blood induced by stimulation with LPS were markedly reduced (P < 0.008) within 3 hr when incubated with IVIG compared to without IVIG. Thus we demonstrated that cells of normal children respond to IVIG in vitro by reducing cytokines such as IL-8, TNF-alpha, and IL-6 without affecting the level of receptor sIL-6R during an acute inflammatory response. We also found significantly higher IL-6 levels in children with Kawasaki disease compared to children with blood culture-negative febrile illnesses. In five children with Kawasaki disease we measured serum IL-6 before and after IVIG and assessed the clinical response to IVIG therapy. Therapy with IVIG was followed by a rapid resolution of symptoms in Kawasaki disease, with a significant decrease in serum IL-6. The attenuation of proinflammatory cytokine responses, especially IL-6, following infusions of IVIG may play an integral role in the rapid resolution of symptoms and decrease in the acute-phase proteins in children with Kawasaki disease. Cells of normal children were found to respond to the IVIG in a manner similar to that of the Kawasaki children.
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PMID:Cytokine modulation with immune gamma-globulin in peripheral blood of normal children and its implications in Kawasaki disease treatment. 1140 26

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

E5564 is a second-generation synthetic analogue of the lipid A component of endotoxin (lipopolysaccharide [LPS]). The ability of E5564 to block the toxic activity of LPS was assessed in a double-blind, placebo-controlled study. A bolus infusion of endotoxin (4 ng/kg) was administered to healthy subjects to induce a mild transient syndrome similar to clinical sepsis. Single E5564 doses of 50-250 microg ameliorated or blocked all of the effects of LPS in a dose-dependent manner. All E5564 dose groups had statistically significant reductions in elevated temperature, heart rate, C-reactive protein levels, white blood cell count, and cytokine levels (tumor necrosis factor-alpha and interleukin-6), compared with placebo (P<.01). In doses of > or = 100 microg, E5564 acted as an LPS antagonist and completely eliminated these signs. E5564 also blocked or ameliorated LPS-induced fever, chills, headache, myalgia, and tachycardia (P<.01). These results demonstrate that E5564 blocks the effects of LPS in a human model of clinical sepsis and indicate its potential in the treatment and/or prevention of clinical sepsis.
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PMID:Blocking of responses to endotoxin by E5564 in healthy volunteers with experimental endotoxemia. 1259 80

Cancer remains the second leading cause of death, after cardiovascular diseases, in industrialized countries. The first goal to achieve is to prevent cancer occurrence or to diagnose it at an early and curable stage. Some screening strategies have been developed, with controversies across countries, for several cancer type; colorectal, breasts or prostate cancer for example.Treatment of cancer is generally based on surgery and radiotherapy for localized and attainable tumors, associated, in some cases, with adjuvant chemotherapy. Chemotherapy can also be used as first line treatment for disseminated diseases.The formulation of therapeutic strategies to enhance immune-mediated tumor destruction is a central goal of cancer immunology. Substantive progress toward delineating the mechanisms involved in innate and adaptive tumor immunity has improved the prospects for crafting efficacious treatments LPS and their active component lipid A, have been used in tumor therapy since the 19th century.Studies in animal models have shown promising results on different models of cancer but data from human trial are scarce. The published Phase-1 cancer studies have shown that lipid A analogues are usually well tolerated, most of the side effects being likely related to immune response, i. e., fever, chills and rigor. The administration of several lipids A analogues was shown to result in a significant increase in circulating levels of several cytokines but no objective antitumor responses were observed. Therefore clinical activity of such molecules deserves further experiments, likely in conjunction with chemotherapy.
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PMID:Antitumoral effects of lipids A, clinical studies. 2066 5