Balance Between Pro- and Anti-Inflammatory Cytokines in Mice Treated With <i>Centruroides noxius</i> Scorpion Venom

Petricevich, Vera L.

doi:https://doi.org/10.1155/MI/2006/54273

Mediators of Inflammation

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Research Communication | Open Access

Volume 2006 | Article ID 054273 | https://doi.org/10.1155/MI/2006/54273

Balance Between Pro- and Anti-Inflammatory Cytokines in Mice Treated With Centruroides noxius Scorpion Venom

Vera L. Petricevich¹

Received21 Jun 2006

Revised10 Sept 2006

Accepted11 Sept 2006

Published09 Nov 2006

Abstract

CSV consists of a very complex of molecules and demonstrates significant cellular activities capable of stimulating immune functions in vivo. The purpose of this study was to analyze the effects of CSV on sex, weight, route of injection and the balance of pro- and anti-inflammatory cytokines in mice. The susceptibility and route of injection were analyzed by lethal (LD50) determination. The effects of CSV were also analyzed in blood from immunized mice using detection by means of antibodies and mediators production. Several functional bioassays were employed: TNF activity was assayed by measuring its cytotoxic activity in L929 cells, and other cytokines were assayed by enzyme-linked immunosorbent assay, whereas nitric oxide levels were detected by Griess colorimetric reactions in sera from BALB/c mice. After injecting subcutaneously, the LD50 presented an increase of the CSV correlation and similar levels of susceptibility were obtained for female and male from BALB/c mice. Significant differences were observed in the time-course of cytokine levels. The balance of pro- and anti-inflammatory cytokines TNF/IL-10 and IL-6/IL-10 ratios were significantly higher in injected mice group when compared with those obtained for non-injected group. The CSV is poor in antigenic composition and it is difficult to get antibodies specific to neutralizing the lethal factor. The effect of immunization with 0.5 LD50 of CSV on the balance of pro- and anti-inflammatory cytokines was measured. The maximum levels of TNF and IL-6, IFN-γ and NO were observed on days 7 and 21 after immunization, respectively. IL-10 levels peaked between days 21 and 28 after immunization with CSV. With respect, to balance of pro- and anti-inflammatory cytokines it was possible to observe that negative correlation between serum levels of IL-6/IL-10 and TNF/IL-10 exists. These ratios may possibly reflect the balance of pro- and anti-inflammatory cytokines in serum, which may by manifested in the inflammatory status during the envenoming processes. In conclusion, an increase in the serum levels of TNF and IL-6 may be a useful marker for scorpion envenomation.

References

M Ismail, “The treatment of the scorpion envenoming syndrome: the Saudi experience with serotherapy,” Toxicon, vol. 32, no. 9, pp. 1019–1026, 1994.
View at: Publisher Site | Google Scholar
M M Magalhães, M ES Pereira, C FS Amaral et al., “Serum levels of cytokines in patients envenomed by Tityus serrulatus scorpion sting,” Toxicon, vol. 37, no. 8, pp. 1155–1164, 1999.
View at: Publisher Site | Google Scholar
V L Petricevich, “Cytokine and nitric oxide production following severe envenomation,” Current Drug Targets: Inflammation and Allergy, vol. 3, no. 3, pp. 325–332, 2004.
View at: Publisher Site | Google Scholar
S Sofer, “Scorpion envenomation,” Intensive Care Medicine, vol. 21, no. 8, pp. 626–628, 1995.
View at: Publisher Site | Google Scholar
A O'Garra, “Cytokines induce the development of functionally heterogeneous T helper cell subsets,” Immunity, vol. 8, no. 3, pp. 275–283, 1998.
View at: Publisher Site | Google Scholar
S Romagnani, “Lymphokine production by human T cells in disease states,” Annual Review of Immunology, vol. 12, pp. 227–257, 1994.
View at: Publisher Site | Google Scholar
J T van Dissel, P van Langevelde, R GJ Westendorp, K Kwappenberg, and M Frölich, “Anti-inflammatory cytokine profile and mortality in febrile patients,” Lancet, vol. 351, no. 9107, pp. 950–953, 1998.
View at: Publisher Site | Google Scholar
T Jo, N Terada, Y Takauchi et al., “Cytotoxic actions of cytokines on cultured mouse luteal cells are independent of nitric oxide,” Journal of Steroid Biochemistry and Molecular Biology, vol. 55, no. 3-4, pp. 291–296, 1995.
View at: Publisher Site | Google Scholar
P H van der Meide and H Schellekens, “Cytokines and the immune response,” Biotherapy, vol. 8, no. 3-4, pp. 243–249, 1996.
View at: Publisher Site | Google Scholar
C Gerard, C Bruyns, A Marchant et al., “Interleukin 10 reduces the release of tumor necrosis factor and prevents lethality in experimental endotoxemia,” Journal of Experimental Medicine, vol. 177, no. 2, pp. 547–550, 1993.
View at: Publisher Site | Google Scholar
M Howard, T Muchamuel, S Andrade, and S Menon, “Interleukin 10 protects mice from lethal endotoxemia,” Journal of Experimental Medicine, vol. 177, no. 4, pp. 1205–1208, 1993.
View at: Publisher Site | Google Scholar
M J Herbertson, H A Werner, C M Goddard et al., “Anti-tumor necrosis factor- $a$ prevents decreased ventricular contractility in endotoxemic pigs,” American Journal of Respiratory and Critical Care Medicine, vol. 152, no. 2, pp. 480–488, 1995.
View at: Google Scholar
B E Barton, “IL-6: insights into novel biological activities,” Clinical Immunology and Immunopathology, vol. 85, no. 1, pp. 16–20, 1997.
View at: Publisher Site | Google Scholar
M C Ruzek, A H Miller, S M Opal, B D Pearce, and C A Biron, “Characterization of early cytokine responses and an interleukin (IL)-6- dependent pathway of endogenous glucocorticoid induction during murine cytomegalovirus infection,” Journal of Experimental Medicine, vol. 185, no. 7, pp. 1185–1192, 1997.
View at: Publisher Site | Google Scholar
Z Xing, J Gauldie, G Cox et al., “IL-6 is an antiinflammatory cytokine required for controlling local or systemic acute inflammatory responses,” Journal of Clinical Investigation, vol. 101, no. 2, pp. 311–320, 1998.
View at: Google Scholar
F Ceciliani, A Giordano, and V Spagnolo, “The systemic reaction during inflammation: the acute-phase proteins,” Protein and Peptide Letters, vol. 9, no. 3, pp. 211–223, 2002.
View at: Publisher Site | Google Scholar
Committe Members. International Society on Toxicology, Toxicon, vol. 30, pp. 1–12, 1992.
V CBC Gebara, V L Petricevich, I Raw, and W Dias da Silva, “Effect of saponin from Quillaja saponaria (molina) on antibody, tumour necrosis factor and interferon- $γ$ production,” Biotechnology and Applied Biochemistry, vol. 22, no. pt 1, pp. 31–37, 1995.
View at: Google Scholar
J R Schumacher, A O'Garra, P Schrader et al., “Characterization of 4 monoclonal antibodies to mouse interleukin-5 and development of mouse and human IL-5 ELISA assays,” Journal of Immunology, vol. 141, no. 5, pp. 1575–1581, 1995.
View at: Google Scholar
M R Ruff and G E Gifford, “Purification and physico-chemical characterization of rabbit tumor necrosis factor,” Journal of Immunology, vol. 125, no. 4, pp. 1671–1677, 1980.
View at: Google Scholar
H HHW Schmidt, R Seifert, and E Bohme, “Formation and release of nitric oxide from human neutrophils and HL-60 cells induced by a chemotactic peptide, platelet activating factor and leukotriene B4,” FEBS Letters, vol. 244, no. 2, pp. 357–360, 1989.
View at: Publisher Site | Google Scholar
M Ismail, “The scorpion envenoming syndrome,” Toxicon, vol. 33, no. 7, pp. 825–858, 1995.
View at: Publisher Site | Google Scholar
E Kalapothakis and C Chávez-Olórtegui, “Venom variability among several Tityus serrulatus specimens,” Toxicon, vol. 35, no. 10, pp. 1523–1529, 1997.
View at: Publisher Site | Google Scholar
D Hoffman, “Insect venom allergy, immunology, and immunotherapy,” in Handbook of Neural Toxins: Insect Poisons, Allergens, and Other Invertebrate Venoms, A T Tu, Ed., vol. 2, pp. 187–224, Marcel Dekker, New York, NY, 1984.
View at: Google Scholar
V L Petricevich and C F Peña, “The dynamics of cytokine d nitric oxide secretion in mice injected with Tityus serrulatus scorpion venom,” Mediators of Inflammation, vol. 11, no. 3, pp. 173–180, 2002.
View at: Publisher Site | Google Scholar
S F Barros, I Friedlanskaia, V L Petricevich, and T L Kipnis, “Local inflammation, lethality and cytokine release in mice injected with Bothrops atrox venom,” Mediators of Inflammation, vol. 7, no. 5, pp. 339–346, 1998.
View at: Publisher Site | Google Scholar
V L Petricevich, C FP Teixeira, D V Tambourgi, and J M Gutiérrez, “Increments in serum cytokine and nitric oxide levels in mice injected with Bothrops asper and Bothrops jararaca snake venoms,” Toxicon, vol. 38, no. 9, pp. 1253–1266, 2000.
View at: Publisher Site | Google Scholar
D V Tambourgi, V L Petricevich, F C Magnoli, S LMR Assaf, S Jancar, and W Dias da Silva, “Endotoxemic-like shock induced by Loxosceles spider venoms: pathological changes and putative cytokine mediators,” Toxicon, vol. 36, no. 2, pp. 391–403, 1998.
View at: Publisher Site | Google Scholar
B Lomonte, A Tarkowski, and L A Hanson, “Host response to Bothrops asper snake venom. Analysis of edema formation, inflammatory cells, and cytokine release in a mouse model,” Inflammation, vol. 17, no. 2, pp. 93–105, 1993.
View at: Publisher Site | Google Scholar
N A De Rezende, M B Dias, D Campolina, C Chavez-Olortegui, C R Diniz, and C FS Amaral, “Efficacy of antivenom therapy for neutralizing circulating venom antigens in patients stung by Tityus serrulatus scorpions,” American Journal of Tropical Medicine and Hygiene, vol. 52, no. 3, pp. 277–280, 1995.
View at: Google Scholar
A Muraguchi, T Hirano, B Tang et al., “The essential role of B cell stimulatory factor 2 (BSF-2/IL-6) for the terminal differentiation of B cells,” Journal of Experimental Medicine, vol. 167, no. 2, pp. 332–344, 1988.
View at: Publisher Site | Google Scholar
Y Takai, G G Wong, S C Clark, S J Burakoff, and S H Herrmann, “B cell stimulatory factor-2 is involved in the differentiation of cytotoxic T lymphocytes,” Journal of Immunology, vol. 140, no. 2, pp. 508–512, 1988.
View at: Google Scholar
J Gauldie, C Richards, D Harnish, P Lansdorp, and H Baumann, “Interferon $β$ 2/B-cell stimulatory factor type 2 shares identity with monocyte-derived hepatocyte-stimulating factor and regulates the major acute phase protein response in liver cells,” Proceedings of the National Academy of Sciences of the United States of America, vol. 84, no. 20, pp. 7251–7255, 1987.
View at: Publisher Site | Google Scholar
L Borish, R Rosenbaum, L Albury, and S Clark, “Activation of neutrophils by recombinant interleukin 6,” Cellular Immunology, vol. 121, no. 2, pp. 280–289, 1989.
View at: Publisher Site | Google Scholar
Y Fong, K J Tracey, L L Moldawer et al., “Antibodies to cachectin/tumor necrosis factor reduce interleukin 1 $ß$ and interleukin 6 appearance during lethal bacteremia,” Journal of Experimental Medicine, vol. 170, no. 5, pp. 1627–1633, 1989.
View at: Publisher Site | Google Scholar
C Haworth, F M Brennan, D Chantry, M Turner, R N Maini, and M Feldmann, “Expression of granulocyte-macrophage colony-stimulating factor in rheumatoid arthritis: regulation by tumor necrosis factor- $α$ ,” European Journal of Immunology, vol. 21, no. 10, pp. 2575–2579, 1991.
View at: Google Scholar
L Lepore, M Pennesi, S Saletta, S Perticarari, G Presani, and M Prodan, “Study of IL-2, IL-6, TNF $α$ , IFN $γ$ and $β$ in the serum and synovial fluid of patients with juvenile chronic arthritis,” Clinical and Experimental Rheumatology, vol. 12, no. 5, pp. 561–565, 1994.
View at: Google Scholar
K W Moore, A O'Garra, R W Malefyt, P Vieira, and T R Mosmann, “Interleukin-10,” Annual Review of Immunology, vol. 11, pp. 165–190, 1993.
View at: Publisher Site | Google Scholar
A Marchant, J Devière, B Byl, D De Groote, J.-L Vincent, and M Goldman, “Interleukin-10 production during septicaemia,” Lancet, vol. 343, no. 8899, pp. 707–708, 1994.
View at: Publisher Site | Google Scholar
H A Young and J R Ortaldo, “One-signal requirement for interferon- $γ$ production by human large granular lymphocytes,” Journal of Immunology, vol. 139, no. 3, pp. 724–727, 1987.
View at: Google Scholar
C A Dinarello, J G Cannon, and S M Wolff, “New concepts on the pathogenesis of fever,” Reviews of Infectious Diseases, vol. 10, no. 1, pp. 168–189, 1988.
View at: Google Scholar
S Okusawa, J A Gelfand, T Ikejima, R J Connolly, and C A Dinarello, “Interleukin 1 induces a shock-like state in rabbits. Synergism with tumor necrosis factor and the effect of cyclooxygenase inhibition,” Journal of Clinical Investigation, vol. 81, no. 4, pp. 1162–1172, 1988.
View at: Google Scholar
D G Remick, R M Strieter, M K Eskandari et al., “Role of tumor necrosis factor- $a$ in lipopolysaccharide-induced pathologic alterations,” American Journal of Pathology, vol. 136, no. 1, pp. 49–60, 1990.
View at: Google Scholar
T van der Poll, J Jansen, M Levi, H ten Cate, J W ten Cate, and S JH van Deventer, “Regulation of interleukin 10 release by tumor necrosis factor in humans and chimpanzees,” Journal of Experimental Medicine, vol. 180, no. 5, pp. 1985–1988, 1994.
View at: Publisher Site | Google Scholar

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Copyright © 2006 Vera L. Petricevich. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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