Title: A Randomized Controlled Study to Assess the Effect of Doxycycline on IL-6 and TNF Levels among the Patients of Dengue
Authors: Dr Nishant Kanodia MBBS MD Medicine, Dr Dinesh Chand Khare MBBS MD Medicine
DOI: https://dx.doi.org/10.18535/jmscr/v6i2.168
Abstract
Objective: To evaluate the ability of doxycycline to modulate cytokines in patients with DF or DHF.
Methods: This was a randomized controlled trial conducted in a tertiary care hospital in north India. A total of 36 patients of DF or DHF were included in the study and randomized into 2 groups (18 in each group) by using computer generated random number table. Blood samples were obtained from hospitalized patients 18–55 years of age presenting with symptoms characteristic of DF or DHF. In group A, for patients 18–55 years of age, an initial oral dose of 200 mg was followed by 100 mg administered at 12 hour intervals for 10 days. Patients of Group B were untreated. Cytokine levels were assessed at 0 day and 7 days by standard methods.
Results: All patients demonstrated elevated IL-6 and TNF levels at day 0 evidenced by higher mean levels in both the groups. Over the 7-day observation period, IL-6 and TNF remained elevated in the control group (Group B). Treatment with doxycycline resulted in statistically (p=0.0001) lower levels of IL-6 and TNF by day 7, both when compared to that seen at day 0 (intragroup analysis) and when compared to day 0 values in the control group. Decreases in Il-6 and TNF between day 0 and day 7 values were modest in the control group than treated with doxycycline (Group A). Treatment with doxycycline resulted in IL-6 and TNF levels being significantly (p=0.0001) lower than control group by day 7.
Conclusions: The findings from the current study indicate that doxycycline could be an effective treatment for dengue patients with high risk of complications.
Keywords: Doxycycline, Dengue, Cytokines.
References
- World Health Organization.Handbook for clinical management of dengue. Geneva: WHO; 2012. p. 4.
- deAzeredo EL, Monteiro RQ, Pinto LM. Thrombocytopenia in dengue: interrelationship between virus and the imbalance between coagulation and fibrinolysis and inflammatory mediators. Mediators Inflamm. 2015.
- World Health Organization. Comprehensive guidelines for prevention and control of dengue and dengue hemorrhagic fever.Revised and expanded edition.Regional Office for South East Asia of the World Health Organization. 2011.
- Marty A. M., Jahrling P. B., and Geisbert T. W. Viral hemorrhagic fevers.Clinics in Laboratory Medicine, vol. 26, no. 2, pp. 345–386, 2006.
- Atrasheuskaya A. V., Fredeking T. M., and Ignatyev G. M.Changes in immune parameters and their correction in human cases of tick-borne encephalitis.Clinical and Experimental Immunology, vol. 131, no. 1, pp. 148–154, 2003.
- Bozza F. A., Cruz O. G., Zagne S. M. O. et al. Multiplex cytokine profile from dengue patients: MIP-1beta and IFN gamma as predictive factors for severity. BMC Infectious Diseases, vol. 8, pp. 86–93, 2008.
- Suharti C., van Gorp E. C. M., Setiati T. E. et al. The role of cytokines in activation of coagulation and fibrinolysis in dengue shock syndrome. Thrombosis and Haemostasis, vol. 87, no. 1, pp. 42–46, 2002.
- Feldmann M. Many cytokines are very useful therapeutic targets in disease. Journal of Clinical Investigation, vol. 118, no. 11, pp. 3533–3536, 2008.
- Tauber S. C. and Nau R. Immunomo-dulatory properties of antibiotics. Current Molecular Pharmacology, vol. 1, no. 1, pp. 68–79, 2008.
- Lai A. Y. and Todd K. G. Hypoxia-activated microglial mediators of neuronal survival are differentially regulated by tetracyclines. GLIA, vol. 53, no. 8, pp. 809–816, 2006.
- Simmons CP, Popper S, Dolocek C, Chau TN, Griffiths M, Dung NT, et al. Patterns of host genomewide gene transcript abundance in the peripheral blood of patients with acute dengue hemorrhagic fever. J Infect Dis 2007; 195: 1097-107.
- Rothan HA, Buckle MJ, Ammar YA, Mohammadjavad P, Shatrah O, Noorsaadah AR, et al. Study the antiviral activity of some derivatives of tetracycline and non-steroid anti inflammatory drugs towards dengue virus. Trop Biomed 2013; 30: 681-90.
- Castro JEZ, Vado-Solis I, Perez-Osorio C, Fredeking TM. Modulation of cytokine and cytokine receptor/antagonist by treatment with doxycycline and tetracycline in patients with dengue fever. Clin Devel Immunol 2011; 2011: 370872.
- Girardin E., Roux-Lombard P., Grau G. E. et al. Imbalance between tumour necrosis factoralpha and soluble TNF receptor concentrations in severe meningococcaemia. Immunology, vol. 76, no. 1, pp. 20–23, 1992.
- Hober D., Poli L., Roblin B. et al. Serum levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-1β (IL-1β) in dengue-infected patients. American Journal of Tropical Medicine and Hygiene, vol. 48, no. 3, pp. 324–331, 1993.
- Yang J. M., Chen Y. F., Tu Y. et al. Combinatorial computational approaches to identify tetracycline derivatives as flavivirus inhibitors. PLoS ONE, vol. 2, no. 5, pp. e428–e441, 2007.