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| IJCEM Copyright © 2008-All rights reserved. Published by e-Century Publishing Corporation, Madison, WI 53711 |
Int J Clin Exp Med 2012;5(1):1-23
Review Article
The role of immunostimulatory nucleic acids in septic shock
Farag Bleiblo, Paul Michael, Danielle Brabant, Chilakamarti V Ramana, TC Tai, Mazen Saleh, Joseph E Parrillo, Anand Kumar, Aseem
Kumar
Department of Chemistry and Biochemistry and the Biomolecular Sciences Programme1, Laurentian University, Sudbury, ON, Canada,
P3E 2C6. Department of Medicine2, Yale University, New Haven, CT, USA, 06516. Division of Cardiovascular Disease and Critical
Care Medicine3, Cooper University Hospital, Robert Wood Johnson Medical School, Camden, New Jersey, USA, 08103. Section of
Critical Care Medicine4, University of Manitoba, Winnipeg, MB, Canada, R3A 1R9.
Received December 20, 2011; accepted January 8, 2012; Epub January 15, 2012; published January 31, 2012
Abstract: Sepsis and its associated syndromes represent the systemic host response to severe infection and is manifested by varying
degrees of hypotension, coagulopathy, and multiorgan dysfunction. Despite great efforts being made to understand this condition and
designing therapies to treat sepsis, mortality rates are still high in septic patients. Characterization of the complex molecular signaling
networks between the various components of host-pathogen interactions, highlights the difficulty in identifying a single driving force
responsible for sepsis. Although triggering the inflammatory response is generally considered as protective against pathogenic
threats, the interplay between the signaling pathways that are induced or suppressed during sepsis may harm the host. Numerous
surveillance mechanisms have evolved to discriminate self from foreign agents and accordingly provoke an effective cellular response
to target the pathogens. Nucleic acids are not only an essential genetic component, but sensing their molecular signature is also an
important quality control mechanism which has evolved to maintain the integrity of the human genome. Evidence that has accumulated
recently indicated that distinct pattern recognition receptors sense nucleic acids released from infectious organisms or from damaged
host cells, resulting in the modulation of intracellular signalling cascades. Immunoreceptor-mediated detection of these nucleic acids
induces antigen-specific immunity, secretion of proinflammatory cytokines and reactive oxygen/nitrogen species and thus are
implicated in a range of diseases including septic shock. (IJCEM1112008)
Keywords: Sepsis, septic shock, immunostimulatory nucleic acid, signaling networks, therapy
Address all correspondence to:
Aseem Kumar, PhD
Department of Chemistry and Biochemistry
Biomolecular Sciences Programme
Laurentian University, 935 Ramsey Lake Rd
Sudbury, ON, Canada P3E 2C6.
Tel: 705-675-1151 ext.2103, Fax: 705-675-4844
E-mail: akumar@laurentian.ca
Review Article
The role of immunostimulatory nucleic acids in septic shock
Farag Bleiblo, Paul Michael, Danielle Brabant, Chilakamarti V Ramana, TC Tai, Mazen Saleh, Joseph E Parrillo, Anand Kumar, Aseem
Kumar
Department of Chemistry and Biochemistry and the Biomolecular Sciences Programme1, Laurentian University, Sudbury, ON, Canada,
P3E 2C6. Department of Medicine2, Yale University, New Haven, CT, USA, 06516. Division of Cardiovascular Disease and Critical
Care Medicine3, Cooper University Hospital, Robert Wood Johnson Medical School, Camden, New Jersey, USA, 08103. Section of
Critical Care Medicine4, University of Manitoba, Winnipeg, MB, Canada, R3A 1R9.
Received December 20, 2011; accepted January 8, 2012; Epub January 15, 2012; published January 31, 2012
Abstract: Sepsis and its associated syndromes represent the systemic host response to severe infection and is manifested by varying
degrees of hypotension, coagulopathy, and multiorgan dysfunction. Despite great efforts being made to understand this condition and
designing therapies to treat sepsis, mortality rates are still high in septic patients. Characterization of the complex molecular signaling
networks between the various components of host-pathogen interactions, highlights the difficulty in identifying a single driving force
responsible for sepsis. Although triggering the inflammatory response is generally considered as protective against pathogenic
threats, the interplay between the signaling pathways that are induced or suppressed during sepsis may harm the host. Numerous
surveillance mechanisms have evolved to discriminate self from foreign agents and accordingly provoke an effective cellular response
to target the pathogens. Nucleic acids are not only an essential genetic component, but sensing their molecular signature is also an
important quality control mechanism which has evolved to maintain the integrity of the human genome. Evidence that has accumulated
recently indicated that distinct pattern recognition receptors sense nucleic acids released from infectious organisms or from damaged
host cells, resulting in the modulation of intracellular signalling cascades. Immunoreceptor-mediated detection of these nucleic acids
induces antigen-specific immunity, secretion of proinflammatory cytokines and reactive oxygen/nitrogen species and thus are
implicated in a range of diseases including septic shock. (IJCEM1112008)
Keywords: Sepsis, septic shock, immunostimulatory nucleic acid, signaling networks, therapy
Address all correspondence to:
Aseem Kumar, PhD
Department of Chemistry and Biochemistry
Biomolecular Sciences Programme
Laurentian University, 935 Ramsey Lake Rd
Sudbury, ON, Canada P3E 2C6.
Tel: 705-675-1151 ext.2103, Fax: 705-675-4844
E-mail: akumar@laurentian.ca
