Effects of sodium methyldithiocarbamate on selected parameters of innate immunity and clearance of bacteria in a mouse model of sepsis.
OBJECTIVE
Sodium methyldithiocarbamate (SMD), the third most widely used conventional pesticide in the United States, has been reported to inhibit several parameters associated with inflammation and to decrease resistance to infection. In a previous study, survival time was markedly decreased when mice were treated orally with SMD shortly before challenge with a high dose of Escherichia coli (E. coli) that was lethal to most of the control mice. In the present study, we evaluated selected parameters of the innate immune system using a lower challenge dose of E. coli, to determine which (if any) of these parameters reflected continued changes through 24h.


METHODS
Bacterial clearance from the peritoneal cavity, production of chemokines and cytokines, and body temperature were measured.


RESULTS
All these parameters were reduced by SMD up to 12h after bacterial challenge, but the concentration of the anti-inflammatory cytokine IL-10 was increased. Even so, mice in the control and SMD-treated groups cleared most bacteria by 24h. Other parameters (cytokine concentrations and body temperature) were also normal or near normal by 24h. The same dosage of SMD administered intranasally also did not significantly decrease survival. Hypothermia from 16 to 28 h correlated with lethal outcome, but SMD significantly increased hypothermia only at 2 and 4h after challenge.


CONCLUSIONS
In spite of substantial early inhibition by SMD of parameters known to be important for resistance to infection, bacterial clearance and survival were not altered, suggesting immunological reserve and/or rapid recovery after transient effects of SMD.
Department of Basic Sciences, College of Veterinary Medicine, Mississippi State University, Mississippi State, MS 39762, United States.
Wei
W
Tan
Department of Basic Sciences, College of Veterinary Medicine, Mississippi State University, Mississippi State, MS 39762, United States. Electronic address: Stephen.b.pruett@msstate.edu.
Stephen B
SB
Pruett
D000818:Animals; D016207:Cytokines / Q000276:immunology; D004195:Disease Models, Animal; D004926:Escherichia coli / Q000276:immunology; D004927:Escherichia coli Infections / Q000150:complications / Q000276:immunology; D005260:Female; D007113:Immunity, Innate / Q000187:drug effects*; D007962:Leukocytes / Q000187:drug effects / Q000276:immunology / Q000382:microbiology; D051379:Mice; D008810:Mice, Inbred C57BL; D010575:Pesticides / Q000009:adverse effects / Q000276:immunology*; D018805:Sepsis / Q000276:immunology* / Q000382:microbiology*; D013859:Thiocarbamates / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology*
D016207:Cytokines; D010575:Pesticides; D013859:Thiocarbamates; C008435:methyldithiocarbamate