title: An increase in the susceptibility of burned patients to infectious complications due to impaired production of macrophage inflammatory protein 1 alpha.
abstract: Sepsis is a major mortality concern with burned patients, who have an increased susceptibility to infectious complications. PBMC from 41 of 45 severely burned patients (91%) failed to produce macrophage inflammatory protein 1alpha (MIP-1alpha) in cultures, while 2355-6900 pg/ml MIP-1alpha were produced by healthy donor PBMC, stimulation with anti-human CD3 mAb. Healthy chimeras (SCID mice inoculated with healthy donor PBMC) treated with anti-human MIP-1alpha mAb and patient chimeras (SCID mice reconstituted with burned patient PBMC) were susceptible (0% survival) to infectious complications induced by well-controlled cecal ligation and puncture. In contrast, patient chimeras treated with human recombinant MIP-1alpha and healthy chimeras were resistant ( approximately 77-81% survival). Similarly, after anti-mouse CD3 mAb stimulation, splenic mononuclear cells from burned mice (6 h to 3 days after thermal injury) did not produce significant amounts of MIP-1alpha in their culture fluids. Normal mice treated with anti-murine MIP-1alpha mAb and burned mice were susceptible to cecal ligation- and puncture-induced infectious complications, while burned mice treated with murine recombinant MIP-1alpha and normal mice were resistant. Burned patients seemed to be more susceptible to infectious complications when the production of MIP-1alpha was impaired.
authors.affiliation: Department of Internal Medicine, University of Texas Medical Branch, 301 University Boulevard, Galveston, TX 77555, USA.
authors.forename: Makiko
authors.initials: M
authors.lastname: Kobayashi
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Takahashi
authors.forename: Arthur P
authors.initials: AP
authors.lastname: Sanford
authors.forename: David N
authors.initials: DN
authors.lastname: Herndon
authors.forename: Richard B
authors.initials: RB
authors.lastname: Pollard
authors.forename: Fujio
authors.initials: F
authors.lastname: Suzuki
mesh_terms: D000293:Adolescent; D000818:Animals; D002056:Burns / Q000150:complications* / Q000235:genetics / Q000276:immunology*; D002432:Cecum; D002478:Cells, Cultured; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D002648:Child; D002675:Child, Preschool; D002678:Chimera / Q000276:immunology; D004195:Disease Models, Animal; D004198:Disease Susceptibility / Q000276:immunology; D005260:Female; D006801:Humans; D007113:Immunity, Innate / Q000235:genetics; D007223:Infant; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000378:metabolism / Q000637:transplantation; D008026:Ligation / Q000009:adverse effects; D019402:Macrophage Inflammatory Proteins / Q000096:biosynthesis* / Q000097:blood / Q000502:physiology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D016513:Mice, SCID; D011677:Punctures / Q000009:adverse effects; D018805:Sepsis / Q000209:etiology / Q000235:genetics / Q000276:immunology*; D013154:Spleen / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism
chemical_list: D054405:Chemokine CCL3; D054407:Chemokine CCL4; D019402:Macrophage Inflammatory Proteins