title: Clinical and Pathological Findings Associated with Aerosol Exposure of Macaques to Ricin Toxin.
abstract: Ricin is a potential bioweapon that could be used against civilian and military personnel. Aerosol exposure is the most likely route of contact to ricin toxin that will result in the most severe toxicity. Early recognition of ricin exposure is essential if specific antidotes are to be applied. Initial diagnosis will most likely be syndromic, i.e., fitting clinical and laboratory signs into a pattern which then will guide the choice of more specific diagnostic assays and therapeutic interventions. We have studied the pathology of ricin toxin in rhesus macaques exposed to lethal and sublethal ricin aerosols. Animals exposed to lethal ricin aerosols were followed clinically using telemetry, by clinical laboratory analyses and by post-mortem examination. Animals exposed to lethal aerosolized ricin developed fever associated with thermal instability, tachycardia, and dyspnea. In the peripheral blood a marked neutrophilia (without immature bands) developed at 24 h. This was accompanied by an increase in monocytes, but depletion of lymphocytes. Red cell indices indicated hemoconcentration, as did serum chemistries, with modest increases in sodium and blood urea nitrogen (BUN). Serum albumin was strikingly decreased. These observations are consistent with the pathological observations of fluid shifts to the lungs, in the form of hemorrhages, inflammatory exudates, and tissue edema. In macaques exposed to sublethal aerosols of ricin, late pathologic consequences included chronic pulmonary fibrosis, likely mediated by M2 macrophages. Early administration of supportive therapy, specific antidotes after exposure or vaccines prior to exposure have the potential to favorably alter this outcome.
authors.affiliation: Departments of Pediatrics and Microbiology, Louisiana State University School of Medicine, Children's Hospital, 200 Henry Clay Ave, New Orleans, LA 70118, USA. spincu@lsuhsc.edu.
authors.forename: Seth H
authors.initials: SH
authors.lastname: Pincus
authors.affiliation: Lilly Research Laboratories, 355 East Merrill Street, Indianapolis, IN 46285, USA. bhaskaran_manoj@lilly.com.
authors.forename: Manoj
authors.initials: M
authors.lastname: Bhaskaran
authors.affiliation: Kinesis Vaccines, Chicago, IL 60030, USA. rnbrey@kvax.org.
authors.forename: Robert N
authors.initials: RN
authors.lastname: Brey
authors.affiliation: Divisions of Pathology, Veterinary Medicine, and Microbiology, Tulane National Primate Research Center, 18703 Three Rivers Road, Covington, LA 70433, USA. pjdidier@tulane.edu.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Didier
authors.affiliation: Divisions of Pathology, Veterinary Medicine, and Microbiology, Tulane National Primate Research Center, 18703 Three Rivers Road, Covington, LA 70433, USA. ldoyle@tulane.edu.
authors.forename: Lara A
authors.initials: LA
authors.lastname: Doyle-Meyers
authors.affiliation: Divisions of Pathology, Veterinary Medicine, and Microbiology, Tulane National Primate Research Center, 18703 Three Rivers Road, Covington, LA 70433, USA. croy@tulane.edu.|Department of Microbiology and Immunology, Tulane School of Medicine, 1430 Tulane Ave., New Orleans, LA 70112, USA. croy@tulane.edu.
authors.forename: Chad J
authors.initials: CJ
authors.lastname: Roy
mesh_terms: D000280:Administration, Inhalation; D000336:Aerosols; D000818:Animals; D002619:Chemical Warfare Agents / Q000633:toxicity*; D004906:Erythrocyte Count; D037181:Lectins, C-Type / Q000276:immunology; D007958:Leukocyte Count; D007964:Leukocytosis / Q000139:chemically induced; D008168:Lung / Q000187:drug effects* / Q000276:immunology / Q000473:pathology; D008253:Macaca mulatta; D016676:Macrophages, Alveolar / Q000187:drug effects / Q000276:immunology; D008297:Male; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins / Q000276:immunology; D009504:Neutrophils / Q000187:drug effects; D011956:Receptors, Cell Surface / Q000276:immunology; D012131:Respiratory Insufficiency / Q000097:blood / Q000139:chemically induced / Q000276:immunology / Q000473:pathology; D012276:Ricin / Q000633:toxicity*
chemical_list: D000336:Aerosols; D002619:Chemical Warfare Agents; D037181:Lectins, C-Type; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins; D011956:Receptors, Cell Surface; D012276:Ricin
keywords: aerosol exposure; biodefense; ricin; syndromic diagnosis; telemetric monitoring; toxin