Abstract
Studying the cytokine profiles in animal models or patients with sepsis provides an experimental basis for the identification of diagnostic biomarkers and therapeutic targets. In this study, we used a liquid protein chip (LiquiChip), also known as flexible multi-analyte profiling technology, to perform quantitative analyses of several cytokines and chemokines (e.g., IL-1β, IL-2, IL-4, IL-5, IL-6, IL-10, IL-12, TNF-α, IFN-γ, granulocyte-macrophage colony-stimulating factor, keratinocyte chemoattractant, monocyte chemoattractant protein, monokine induced by gamma interferon, IFN-γ-inducible protein 10, and macrophage inflammatory protein 1 alpha). The levels of these cytokines and chemokines were determined both in the blood and in tissues, including the lung, liver, heart, kidney, spleen, brain, stomach, intestine and muscle, of mice challenged with LPS. Our data showed variable production levels of LPS-induced cytokines in different mouse organs, and the cytokine in the blood did not correlate with those in the organs. We also showed that the levels of most cytokines peaked within 1 to 6 h and decreased rapidly afterward. A variety of inflammatory cytokines might be related to the damage in different organs during septic shock. Our data also suggest that the spleen might be an important target organ in the development of systemic inflammatory response syndrome and sepsis.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Abraham, E., Anzueto, A., Gutierrez, G., Tessler, S., Pedro, G.S., Wunderink, R., Nogare, A.D., Nasraway, S., Berman, S., Cooney, R., Levy, H., Baughman, R., Rumbak, M., Light, R.B., Poole, L., Allred, R., Constant, J., Pennington, J., and Porter, S. (1998). Double-blind randomised controlled trial of monoclonal antibody to human tumour necrosis factor in treatment of septic shock. Lancet 351, 929–933.
Akira, S., Uematsu, S., and Takeuchi, O. (2006). Pathogen recognition and innate immunity. Cell 124, 783–801.
Brigham, K.L. and Meyrick, B. (1986). Endotoxin and lung injury. Am Rev Respir Dis 133, 913–927.
Cannon, J.G., Tompkins, R.G., Gelfand, J.A., Michie, H.R., Stanford, G.G., van der Meer, J.W.M., Endres, S., Lonnemann, G., Corsetti, J., Chernow, B., Wilmore, D.W., Wolff, S.M., Burke, J.F., and Dinarello, C.A. (1990). Circulating interleukin-1 and tumor necrosis factor in septic shock and experimental endotoxin fever. J Infect Diss 161, 79–84.
Cantaluppi, V., Quercia, A.D., Dellepiane, S., Ferrario, S., Camussi, G., and Biancone, L. (2014). Interaction between systemic inflammation and renal tubular epithelial cells. Nephrol Dial Transplant 29, 2004–2011.
Cuschieri, J., Bulger, E., Schaeffer, V., Sakr, S., Nathens, A.B., Hennessy, L., Minei, J., Moore, E.E., O’Keefe, G., Sperry, J., Remick, D., Tompkins, R., Maier, R.V., and Maier, R.V. (2010). Early elevation in random plasma IL-6 after severe injury is associated with development of organ failure. Shock 34, 346–351.
Dupont, N.C., Wang, K., Wadhwa, P.D., Culhane, J.F., and Nelson, E.L. (2005). Validation and comparison of luminex multiplex cytokine analysis kits with ELISA: Determinations of a panel of nine cytokines in clinical sample culture supernatants. J Reprod Immunol 66, 175–191.
Goujon, E., Parnet, P., Layé, S., Combe, C., and Dantzer, R. (1996). Adrenalectomy enhances pro-inflammatory cytokines gene expression, in the spleen, pituitary and brain of mice in response to lipopolysaccharide. Mol Brain Res 36, 53–62.
Horeczko, T., Green, J.P., and Panacek, E.A. (2014). Epidemiology of the Systemic Inflammatory Response Syndrome (SIRS) in the emergency department. West J Emerg Med 15, 329–336.
Jawa, R.S., Anillo, S., Huntoon, K., Baumann, H., and Kulaylat, M. (2011). Interleukin-6 in surgery, trauma, and critical care part II: clinical implications. J Intensive Care Med 26, 73–87.
Marshall, J.C. (2006). Biomarkers of sepsis. Curr Infect Dis Rep 8, 351–357.
Marzocco, S., Di Paola, R., Ribecco, M.T., Sorrentino, R., Domenico, B., Genesio, M., Pinto, A., Autore, G., and Cuzzocrea, S. (2004). Effect of methylguanidine in a model of septic shock induced by LPS. Free Radic Res 38, 1143–1153.
Michie, H.R., Manogue, K.R., Spriggs, D.R., Revhaug, A., O’Dwyer, S., Dinarello, C.A., Cerami, A., Wolff, S.M., and Wilmore, D.W. (1988). Detection of circulating tumor necrosis factor after endotoxin administration. N Engl J Med 318, 1481–1486.
O’Garra, A., and Murphy, K. (1994). Role of cytokines in determining T-lymphocyte function. Curr Opin Immunol 6, 458–466.
Opal, S.M., Laterre, P.F., Francois, B., LaRosa, S.P., Angus, D.C., Mira, J.P., Wittebole, X., Dugernier, T., Perrotin, D., Tidswell, M., Jauregui, L., Krell, K., Pachl, J., Takahashi, T., Peckelsen, C., Cordasco, E., Chang, C.S., Oeyen, S., Aikawa, N., Maruyama, T., Schein, R., Kalil, A.C., Van Nuffelen, M., Lynn, M., Rossignol, D.P., Gogate, J., Roberts, M.B., Wheeler, J.L., Vincent, J.L., and ACCESS Study Group, (2013). Effect of eritoran, an antagonist of MD2-TLR4, on mortality in patients with severe sepsis: the ACCESS randomized trial. JAMA 309, 1154.
Panacek, E.A., Marshall, J.C., Albertson, T.E., Johnson, D.H., Johnson, S., MacArthur, R.D., Miller, M., Barchuk, W.T., Fischkoff, S., Kaul, M., Teoh, L., Van Meter, L., Daum, L., Lemeshow, S., Hicklin, G., and Doig, C. (2004). Efficacy and safety of the monoclonal anti-tumor necrosis factor antibody F(ab′)2 fragment afelimomab in patients with severe sepsis and elevated interleukin-6 levels. Crit Care Med 32, 2173–2182.
Poltorak, A., He, X., Smirnova, I., Liu, M.Y., van Huffel, C., Du, X., Birdwell, D., Alejos, E., Silva, M., Galanos, C., Freudenberg, M., Ricciardi-Castagnoli, P., Layton, B., and Beutler, B. (1998). Defective LPS signaling in C3H/HeJ and C57BL/10ScCr mice: mutations in Tlr4 gene. Science 282, 2085–2088.
Qiu, P., Cui, X., Sun, J., Welsh, J., Natanson, C., and Eichacker, P.Q. (2013). Antitumor necrosis factor therapy is associated with improved survival in clinical sepsis trials. Crit Care Med 41, 2419–2429.
Salkowski, C.A., Detore, G., Franks, A., Falk, M.C., and Vogel, S.N. (1998). Pulmonary and hepatic gene expression following cecal ligation and puncture: monophosphoryl lipid A prophylaxis attenuates sepsis-induced cytokine and chemokine expression and neutrophil infiltration. Infect Immun 66, 3569–3578.
Secher, T., Vasseur, V., Poisson, D.M., Mitchell, J.A., Cunha, F.Q., Alves-Filho, J.C., and Ryffel, B. (2009). Crucial role of TNF receptors 1 and 2 in the control of polymicrobial sepsis. J Immunol 182, 7855–7864.
Seeley, E.J., Matthay, M.A., and Wolters, P.J. (2012). Inflection points in sepsis biology: from local defense to systemic organ injury. Am J Physiol Lung Cell Mol Physiol 303, L355–L363.
Seideman, J., and Peritt, D. (2002). A novel monoclonal antibody screening method using the Luminex-100™ microsphere system. J Immunol Methods 267, 165–171.
Shimura, E., Shibui, A., Narushima, S., Nambu, A., Yamaguchi, S., Akitsu, A., Leonard, W.J., Iwakura, Y., Matsumoto, K., Suto, H., Okumura, K., Sudo, K., and Nakae, S. (2014). Potential role of myeloid cell/eosinophilderived IL-17 in LPS-induced endotoxin shock. Biochem Biophys Res Commun 453, 1–6.
Singer, M., Deutschman, C.S., Seymour, C.W., Shankar-Hari, M., Annane, D., Bauer, M., Bellomo, R., Bernard, G.R., Chiche, J.D., Coopersmith, C.M., Hotchkiss, R.S., Levy, M.M., Marshall, J.C., Martin, G.S., Opal, S.M., Rubenfeld, G.D., van der Poll, T., Vincent, J.L., and Angus, D.C. (2016). The third international consensus definitions for sepsis and septic shock (sepsis-3). JAMA 315, 801.
Takahashi, W., Nakada, T.A., Yazaki, M., and Oda, S. (2016). Interleukin-6 levels act as a diagnostic marker for infection and a prognostic marker in patients with organ dysfunction in intensive care units. Shock 46, 254–260.
Tetta, C., Bellomo, R., D’Intini, V., De Nitti, C., Inguaggiato, P., Brendolan, A., and Ronco, C. (2003). Do circulating cytokines really matter in sepsis? Kidney Int 63, S69–S71.
Tsalik, E.L., Jaggers, L.B., Glickman, S.W., Langley, R.J., van Velkinburgh, J.C., Park, L.P., Fowler, V.G., Cairns, C.B., Kingsmore, S.F., and Woods, C.W. (2012). Discriminative value of inflammatory biomarkers for suspected sepsis. J Emerg Med 43, 97–106.
Ulloa, L., and Tracey, K.J. (2005). The “cytokine profile”: a code for sepsis. Trends Mol Med 11, 56–63.
van der Poll, T., and Opal, S.M. (2008). Host-pathogen interactions in sepsis. Lancet Infect Dis 8, 32–43.
van der Poll, T. (2001). Immunotherapy of sepsis. Lancet Infect Dis 1, 165–174.
Vignali, D.A. (2000). Multiplexed particle-based flow cytometric assays. J Immunol Methods 243, 243–255.
Voves, C., Wuillemin, W.A., and Zeerleder, S. (2006). International Society on Thrombosis and Haemostasis score for overt disseminated intravascular coagulation predicts organ dysfunction and fatality in sepsis patients. Blood Coagul Fibrinolysis 17, 445–451.
Wenzel, R.P. (2002). Treating sepsis. N Engl J Med 347, 966–967.
Zeni, F., Freeman, B., and Natanson, C. (1997). Anti-inflammatory therapies to treat sepsis and septic shock. Crit Care Med 25, 1095–1100.
Acknowledgements
This work was supported by the National Natural Science Foundation of China (81471901, 81272149, 181372030, 81671965), the Guangdong Provincial Key Laboratory Construction Project of China (2014B030301044), the Key Scientific and Technological Program of Guangzhou City (201607020016), and the Guangdong Provincial Natural Science Foundation (2015A030311031).
Author information
Authors and Affiliations
Corresponding authors
Rights and permissions
About this article
Cite this article
Liu, J., Wang, J., Luo, H. et al. Screening cytokine/chemokine profiles in serum and organs from an endotoxic shock mouse model by LiquiChip. Sci. China Life Sci. 60, 1242–1250 (2017). https://doi.org/10.1007/s11427-016-9016-6
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11427-016-9016-6