Systemic cytokine response in children bitten by snakes in Costa Rica.
BACKGROUND
To characterize the host response to venom from snakes of the family Viperidae in Costa Rica, we investigated the release of cytokines: IL-1, IL-6, IL-8, TNF-alpha, MIP-1beta, and RANTES in pediatric patients who were bitten by a snake.


METHODS
Patients were included in this study if they were admitted to the hospital within 24 hours of the snakebite. Blood samples were taken immediately on admission to the hospital, and then at intervals of 3, 12, and 24 hours, and on days 3, 5, and 7 after the accident. Patients received gentamicin plus clindamycin or gentamicin plus penicillin intravenously for a minimum of 3 days or longer if necessary. IL-1, IL-8, TNF-alpha, MIP-1beta, and RANTES were determined by monoclonal antibody-based ELISAs, while IL-6 was determined by bioassay.


RESULTS
Eighteen patients were included in this study; 15 were bitten by Bothrops asper and three by B. lateralis. Eleven patients were male. Median (range) age was 9 (1-12) years. Nine patients had detectable serum concentrations of IL-6 (200 pg/ mL) and IL-8 (51 pg/mL) on admission, increasing to 500 pg/mL and 115 pg/mL for IL-6 and IL-8, respectively, during the first 12-24 hours. Cytokine concentrations returned to normal or undetectable ranges by 72 hours. TNF-alpha concentrations peaked at 12 hours (mean: 48 pg/mL). Low, but detectable concentrations of MIP-1beta were observed in some patients at various time intervals (48 pg/mL), whereas IL-1 was not detectable at any time point. Regulated on Activation Normal T cell Expressed and Secreted (RANTES) concentrations were evaluated in only five patients, being elevated in all of them. Patients with elevated cytokine concentrations required early fasciotomy (<24 hours after the accident) more often than those who had normal or undetectable cytokine concentrations (P < 0.05). There were no statistically significant associations between severity of envenomation, or outcome, and elevated serum cytokine concentrations (P > 0.05).


CONCLUSIONS
Bothrops sp snake venoms induce clinical and pathophysiologic alterations similar to acute trauma, with release of proinflammatory cytokines. A better understanding of the role of the inflammatory response could lead to the development of new therapeutic strategies to improve the outcome in snakebitten patients.
Avila-Agüero
M L
ML
Servicio de Infectología, Hospital Nacional de Niños, Universidad de Costa Rica. maluvi@racsa.co.cr
París
M M
MM
Hu
S
S
Peterson
P K
PK
Gutiérrez
J M
JM
Lomonte
B
B
Faingezicht
I
I
D000818:Animals; D000900:Anti-Bacterial Agents / Q000627:therapeutic use; D017837:Bothrops; D018946:Chemokine CCL5 / Q000097:blood; D002648:Child; D002675:Child, Preschool; D002981:Clindamycin / Q000627:therapeutic use; D003364:Costa Rica; D016207:Cytokines / Q000097:blood*; D005208:Fasciitis / Q000209:etiology / Q000517:prevention & control / Q000601:surgery; D005260:Female; D006801:Humans; D007223:Infant; D015850:Interleukin-6 / Q000097:blood; D016013:Likelihood Functions; D008297:Male; D010406:Penicillins / Q000627:therapeutic use; D012720:Severity of Illness Index; D012909:Snake Bites / Q000150:complications / Q000188:drug therapy* / Q000276:immunology*
D000900:Anti-Bacterial Agents; D018946:Chemokine CCL5; D016207:Cytokines; D015850:Interleukin-6; D010406:Penicillins; D002981:Clindamycin