Detection of macrophage inflammatory protein (MIP)-1alpha and MIP-1beta during experimental endotoxemia and human sepsis.
Macrophage inflammatory protein (MIP)-1alpha and MIP-1beta regulate leukocyte activation and trafficking. To assess the role of MIP-1alpha and MIP-1beta in human inflammation, healthy subjects were studied during experimental endotoxemia with prior administration of ibuprofen, a cyclooxygenase inhibitor, or dimeric p75 tumor necrosis factor (TNF)-alpha receptor, a TNF antagonist; septic patients were also studied. Following endotoxin, blood levels of both MIP-1 molecules rose acutely and fell to baseline by 6 h (P=. 001). While MIP-1 mediates fever in animals independent of cyclooxygenase blockade, in subjects given endotoxin and ibuprofen, MIP-1 levels increased and fever was suppressed. MIP-1 levels were not diminished by inhibiting circulating TNF-alpha in humans. In septic patients, elevated levels of MIP-1alpha and MIP-1beta were detected within 24 h of sepsis and fell in parallel with TNF-alpha and interleukin-6 (P<.01). MIP-1alpha and MIP-1beta increase during acute inflammation but are not associated with fever in endotoxemic humans during cyclooxygenase blockade.
O'Grady
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National Institutes of Health, Warren Grant Magnuson Clinical Center, Building 10, Rm 7D-43, 10 Center Drive, MSC-1662, Bethesda, MD 20892- 1662, USA. nogrady@cc.nih.gov
Tropea
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Preas
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Reda
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Vandivier
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Banks
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Suffredini
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D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015703:Antigens, CD / Q000008:administration & dosage; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D002648:Child; D016861:Cyclooxygenase Inhibitors / Q000008:administration & dosage; D019446:Endotoxemia / Q000097:blood* / Q000188:drug therapy / Q000276:immunology*; D005260:Female; D005334:Fever / Q000209:etiology; D006801:Humans; D007052:Ibuprofen / Q000008:administration & dosage; D018836:Inflammation Mediators / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D007700:Kinetics; D019402:Macrophage Inflammatory Proteins / Q000097:blood*; D008297:Male; D008875:Middle Aged; D018124:Receptors, Tumor Necrosis Factor / Q000008:administration & dosage; D047889:Receptors, Tumor Necrosis Factor, Type II; D018805:Sepsis / Q000097:blood* / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000378:metabolism
D015703:Antigens, CD; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D016861:Cyclooxygenase Inhibitors; D018836:Inflammation Mediators; D015850:Interleukin-6; D019402:Macrophage Inflammatory Proteins; D018124:Receptors, Tumor Necrosis Factor; D047889:Receptors, Tumor Necrosis Factor, Type II; D014409:Tumor Necrosis Factor-alpha; D007052:Ibuprofen