Clinical and Pathological Findings Associated with Aerosol Exposure of Macaques to Ricin Toxin

Toxins

Seth H. Pincus⁴  Manoj Bhaskaran¹  Robert N. Brey³  Peter J. Didier²  Lara A. Doyle-Meyers²  Chad J. Roy² 

[1] Lilly Research Laboratories, 355 East Merrill Street, Indianapolis, IN 46285, USA; E-Mail:;Divisions of Pathology, Veterinary Medicine, and Microbiology, Tulane National Primate Research Center, 18703 Three Rivers Road, Covington, LA 70433, USA; E-Mails:;Kinesis Vaccines, Chicago, IL 60030, USA; E-Mail:;Departments of Pediatrics and Microbiology, Louisiana State University School of Medicine, Children’s Hospital, 200 Henry Clay Ave, New Orleans, LA 70118, USA

关键词: ricin;    toxin;    aerosol exposure;    syndromic diagnosis;    biodefense;    telemetric monitoring;   

DOI  :  10.3390/toxins7062121

来源: mdpi

【 摘 要 】

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.

【 授权许可】

CC BY   
© 2015 by the authors; licensee MDPI, Basel, Switzerland.