title: Early onset of virus infection and up-regulation of cytokines in mice treated with cadmium and manganese.
abstract: A substantial database indicates that a large number of environmental pollutants, chemicals and therapeutic agents to which organisms are exposed cause immunotoxicity. The suppression of immune functions may cause increased susceptibility of the host to a variety of microbial pathogens potentially resulting in a life-threatening state. Evaluation of the immunotoxic potential of chemical xenobiotics is of great concern and, therefore, we have investigated the impact of exposure of inorganic metals, specifically cadmium (Cd) and manganese (Mn) on Encephalomyocarditis virus (EMCV), Semliki Forest virus (SFV), and Venezuelan Equine Encephalitis virus (VEEV) infection. Pretreatment with a single, oral dose of Cd or Mn increased the susceptibility of mice to a sub-lethal infection of these viruses as observed by increased severity of symptoms and mortality compared to untreated controls. An early onset of virus infection was found in brains of Cd and Mn treated animals. Histopathological observations of the brain indicate evidence of inflammation and greater tissue pathology in Cd-or Mn-exposed mice compared to control animals. Meningitis and vascular congestion was seen in virus infected mice in all the metal treated groups, and further, the perivascular inflammation appeared earlier in treated mice compared to control. Encephalitis was maximum in Cd pretreated mice. Widespread environmental contamination of metals and the potential for their exposure and subsequent infection of humans or animals is indicative that further studies of these and all other metals are important to understand the effect of environmental pollution on human health.
authors.affiliation: Center for Combat Casualty Care and Life Sustainment Research, Department of Pathology, Uniformed Services University of the Health Sciences (USUHS), Bethesda, MD-20814, USA.
authors.forename: Pankaj
authors.initials: P
authors.lastname: Seth
authors.forename: Mirza M
authors.initials: MM
authors.lastname: Husain
authors.forename: Pratibha
authors.initials: P
authors.lastname: Gupta
authors.forename: A
authors.initials: A
authors.lastname: Schoneboom
authors.forename: Bruce Franziska B
authors.initials: BF
authors.lastname: Grieder
authors.forename: Haresh
authors.initials: H
authors.lastname: Mani
authors.forename: Radha K
authors.initials: RK
authors.lastname: Maheshwari
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000473:pathology / Q000821:virology; D002104:Cadmium / Q000633:toxicity*; D016207:Cytokines / Q000235:genetics*; D004666:Encephalitis Virus, Venezuelan Equine / Q000502:physiology; D005260:Female; D008297:Male; D020149:Manganese Poisoning; D051379:Mice; D008810:Mice, Inbred C57BL; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics; D012672:Semliki forest virus / Q000502:physiology; D015996:Survival Rate; D015854:Up-Regulation / Q000187:drug effects*; D014777:Virus Diseases / Q000235:genetics* / Q000473:pathology / Q000821:virology*
chemical_list: D016207:Cytokines; D012333:RNA, Messenger; D002104:Cadmium