Human cytokine response to Texas crotaline envenomation before and after antivenom administration.
OBJECTIVE
The aim of this study was to characterize the human cytokine response to Texas crotaline envenomation before and after antivenom administration.


METHODS
This study enrolled crotaline bite victims presenting to a regional trauma center and children's hospital from March to November 2007 and age-matched unbitten controls. Blood spot cards were obtained from bite victims at presentation and at 1 and 6 hours after antivenom administration. One control sample was drawn from each of the age-matched controls selected from urgent care patients presenting for minor complaints. Samples were delivered to a laboratory using a proprietary method for quantitative evaluation of a large number of biomarkers in parallel with bead-based multiplex immunoassays.


RESULTS
After obtaining informed consent, 14 crotaline bite victims (age range, 5-85 years; median age, 45 years; 50% female) (Snakebite Severity Score, 2-7; median, 3) and 14 age-matched controls were enrolled. There were 7 copperhead (Agkistrodon contortrix) bites, 4 rattlesnake (probably Western Diamondback Crotalus atrox) bites, 2 cottonmouth (Agkistrodon piscivorus) bites, and 1 bite from a snake that was not identified by the victim. In t tests, the means in the presentation samples for apolipoprotein A-I (Apo A-I), Apo C3, interleukin 4 (IL-4), myeloperoxidase, plasminogen activator inhibitor 1 (PAI-1), epidermal growth factor, and regulated upon activation, normal t-cell expressed and secreted were significantly lower and Apo H was significantly higher in the bite patients than in the controls. In the 1-hour sample, α(1)-antitrypsin, Apo A-I, Apo C3, eotaxin, IL-4, myeloperoxidase, and PAI-1 levels were lower and prostatic acid phosphatase and cancer antigen 125 levels were higher in the bite patients than in the controls. And in the 6-hour sample, α(1)-antitrypsin, Apo A-I, Apo C3, endothelin-1, IL-4, macrophage inflammatory protein 1β, myeloperoxidase, and epidermal growth factor levels were lower and Apo H level was higher in the bite patients than in controls (all P values < .05).


CONCLUSIONS
Crotaline venom produces a broad cytokine response in human bite victims. In particular, IL-4, myeloperoxidase, and Apo A-I and C3 levels remain altered despite antivenom therapy, whereas PAI-1 and regulated upon activation, normal t-cell expressed and secreted levels seem to normalize after antivenin as other markers are affected. Understanding this profile and further study of the markers identified might lead to improved therapies and better prognostic indicators.
Crocker
Patrick
P
Dell Children's Medical Center of Central Texas, USA.
Zad
Omid
O
Milling
Truman
T
Maxson
Todd
T
King
Benjamin
B
Whorton
Elbert
E
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017836:Agkistrodon; D000818:Animals; D000997:Antivenins / Q000276:immunology / Q000627:therapeutic use*; D016632:Apolipoprotein A-I / Q000097:blood; D053305:Apolipoprotein C-III / Q000097:blood; D002648:Child; D002675:Child, Preschool; D003435:Crotalid Venoms / Q000037:antagonists & inhibitors* / Q000276:immunology; D017839:Crotalus; D016207:Cytokines / Q000097:blood* / Q000276:immunology; D004815:Epidermal Growth Factor / Q000097:blood; D005260:Female; D006801:Humans; D015847:Interleukin-4 / Q000097:blood; D008297:Male; D008875:Middle Aged; D009195:Peroxidase / Q000097:blood; D017395:Plasminogen Activator Inhibitor 1 / Q000097:blood; D012909:Snake Bites / Q000276:immunology* / Q000628:therapy; D013781:Texas; D013997:Time Factors; D055815:Young Adult
D000997:Antivenins; D016632:Apolipoprotein A-I; D053305:Apolipoprotein C-III; D003435:Crotalid Venoms; D016207:Cytokines; D017395:Plasminogen Activator Inhibitor 1; D015847:Interleukin-4; D004815:Epidermal Growth Factor; D009195:Peroxidase