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Systemic cytokine response in children bitten by snakes in Costa Rica

ÁVILA-AGÜERO, MARÍA L. MD; PARÍS, MARÍA M. MD; HU, SHUXIAN MD; PETERSON, PHILLIP K. MD; GUTIÉRREZ, JOSÉ MARÍA MQC, PhD; LOMONTE, BRUNO MQC, PhD; FAINGEZICHT, IDIS MD

Original Articles

Background To characterize the host response to venom from snakes of the familyViperidaein Costa Rica, we investigated the release of cytokines: IL-1, IL-6, IL-8, TNF-α, MIP-1β, 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-α, MIP-1β, 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 byBothrops asperand three byB. 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-α concentrations peaked at 12 hours (mean: 48 pg/mL). Low, but detectable concentrations of MIP-1β 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 Bothropssp 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.

Servicio de Infectología, Hospital Nacional de Niños, Universidad de Costa Rica and Universidad Autónoma de Centroamérica (M.L. Ávila-Agüero, M.M. Paris, I. Faingezicht), Institute for Brain and Immune Disorders, Minneapolis Medical Research Foundation, University of Minnesota, USA (S. Hu, P.K. Peterson), and Instituto Clodomiro Picado, Facultad de Microbiología, Universidad de Costa Rica, San José, Costa Rica (J.M. Gutiérrez, B. Lomonte).

Address for reprints: María L. Ávila-Agüero, MD, Pediatric Infectious Diseases, SJO 1978 PO Box 025216, Miami FL 33102-5216; e-email: maluvi@racsa.co.cr; mavila@hnn.sa.cr

The Snakebite Study Group: Fernando Mora, MD, Rolando Ulloa, MD, Kathia Valverde, MD (Hospital Nacional de Niños), Viviana Beita, MD (Hospital Escalante Pradilla), and Claudio R Ávila-Agüero, MQC (Hospital Monseñor Sanabria).

We thank Dr. Octavio Ramilo from Southwestern Medical Center at Dallas for his critical review of this manuscript. We are indebted to all patients participating in this study.

© 2001 Lippincott Williams & Wilkins, Inc.