Skip to main content
Erschienen in: Inflammation 4-6/2005

01.12.2005

Role of Interleukin-6 in Immune Complex Induced Models of Vascular Injury

verfasst von: Shannon D. McClintock, Adam G. Barron, Eric W. Olle, Michael P. Deogracias, Roscoe L. Warner, Mark Opp, Kent J. Johnson

Erschienen in: Inflammation | Ausgabe 4-6/2005

Einloggen, um Zugang zu erhalten

Abstract

Previous studies have suggested that Interleukin-6 (IL-6) acts as a marker of vasculitis. To determine the role of IL-6 in vasculitis we utilized two models of immune complex induced vascular injury (dermal Arthus and acute pulmonary alveolitis) in IL-6 deficient (IL-6−/−) and IL-6 sufficient (IL-6+/+) mice. Plasma and bronchoalveolar lavage (BAL) levels of IL-6 were elevated in the injured IL-6+/+ mice with acute alveolitis and in the plasma of IL-6+/+ mice with dermal Arthus vasculitis. While, IL-6 levels in IL-6−/− mice were near or below the levels of detection. Histological examination of the intensity of vascular injury response demonstrated no significant differences between IL-6−/− and IL6+/+ mice. More specifically, lung permeability (total protein in the BAL) in the lung injury model in IL-6−/− mice was the same as injured IL-6+/+ mice. As a corollary, assessment of vascular permeability in both models was the same in the IL-6−/− as the IL-6+/+ mice. Quantification of leukocyte influx into the injured tissues in both models also revealed no differences between the IL-6−/− and IL-6+/+ mice. These data demonstrate that while IL-6 is upregulated in acute vascular injury it does not appear to be critical in the development of the vascular inflammatory response.
Literatur
1.
Zurück zum Zitat Heinrich, P. C., R. Behrmann, S. Haan, H. M. Hermanns, G. Muller-Newen, and F. Schaper. 2003. Review article. Principles of interleukin (IL)-6-type cytokine signaling and its regulation. Biochem. J. 15(374(Pt 1)):1–20.CrossRef Heinrich, P. C., R. Behrmann, S. Haan, H. M. Hermanns, G. Muller-Newen, and F. Schaper. 2003. Review article. Principles of interleukin (IL)-6-type cytokine signaling and its regulation. Biochem. J. 15(374(Pt 1)):1–20.CrossRef
2.
Zurück zum Zitat Tackey, E., P. E. Lipsky, and G. G. Illei. 2004. Rationale for interleukine-6 blockade in systemic lupus erythematosus. Lupus. 13(5):339–343.PubMedCrossRef Tackey, E., P. E. Lipsky, and G. G. Illei. 2004. Rationale for interleukine-6 blockade in systemic lupus erythematosus. Lupus. 13(5):339–343.PubMedCrossRef
3.
Zurück zum Zitat Naka, T., N. Nishimoto, and T. Kishimoto. 2002. The paradigm of IL-6: from basic science to medicine. Arthritis Res. 4(Suppl 3):S233–S242.PubMedCrossRef Naka, T., N. Nishimoto, and T. Kishimoto. 2002. The paradigm of IL-6: from basic science to medicine. Arthritis Res. 4(Suppl 3):S233–S242.PubMedCrossRef
4.
Zurück zum Zitat Sundy, J. S., and B. F. Haynes. 2000. Cytokines and adhesion molecules in the pathogenesis of vasculitis. Curr. Rheumatol. Rep. 2(5):402–410.PubMed Sundy, J. S., and B. F. Haynes. 2000. Cytokines and adhesion molecules in the pathogenesis of vasculitis. Curr. Rheumatol. Rep. 2(5):402–410.PubMed
5.
Zurück zum Zitat Chodorowska, G., and D. Czelej. 2003. Drug-induced hyperalergic vasculitis-activity of selected cytokines and acute phase proteins in plasma. Ann. Univ. Mariae Curie-Sklodowska Sect D, Med. 58(1):43–47. Chodorowska, G., and D. Czelej. 2003. Drug-induced hyperalergic vasculitis-activity of selected cytokines and acute phase proteins in plasma. Ann. Univ. Mariae Curie-Sklodowska Sect D, Med. 58(1):43–47.
6.
Zurück zum Zitat Ohlsson, S., J. Wieslander, and M. Segelmark. 2004. Circulating cytokine profile in anti-neutrophilic cytoplasmatic autoantibody-associated vasculitis. Prediction of outcome? Mediat. Inflamm. 13(4):275–283.CrossRef Ohlsson, S., J. Wieslander, and M. Segelmark. 2004. Circulating cytokine profile in anti-neutrophilic cytoplasmatic autoantibody-associated vasculitis. Prediction of outcome? Mediat. Inflamm. 13(4):275–283.CrossRef
7.
Zurück zum Zitat Nalbant, S., B. Koc, C. Top, Y. Kucukardali, Y. Baykai, M. Danaci, and I. H. Kocer. 2002. Hypersensivity vasculitis and cytokines. Rheumatol. Int. 22(6):244–248.PubMedCrossRef Nalbant, S., B. Koc, C. Top, Y. Kucukardali, Y. Baykai, M. Danaci, and I. H. Kocer. 2002. Hypersensivity vasculitis and cytokines. Rheumatol. Int. 22(6):244–248.PubMedCrossRef
8.
Zurück zum Zitat Goronzy, J. J., and C. M. Weyand. 2002. Cytokines in giant-cell arteritis. Review. Clevel. Clin. J Med. 69(Suppl 2):S1191–S11914. Goronzy, J. J., and C. M. Weyand. 2002. Cytokines in giant-cell arteritis. Review. Clevel. Clin. J Med. 69(Suppl 2):S1191–S11914.
9.
Zurück zum Zitat Muller Kobold, A. C., and C. G. Kallenberg. 1999. Monocyte activation in patients with Wegener’s granulomatosis. Ann. Rheum. Dis. 58(4):237–245.PubMedCrossRef Muller Kobold, A. C., and C. G. Kallenberg. 1999. Monocyte activation in patients with Wegener’s granulomatosis. Ann. Rheum. Dis. 58(4):237–245.PubMedCrossRef
10.
Zurück zum Zitat Tomer, Y., V. Barak, B. Bilburd, and Y. Shoenfeld. 1999. Cytokines in experimental autoimmune vasculitis. Evidence for a Th2 type response. Clin. Exp. Rheumatol. 17(5):521–526.PubMed Tomer, Y., V. Barak, B. Bilburd, and Y. Shoenfeld. 1999. Cytokines in experimental autoimmune vasculitis. Evidence for a Th2 type response. Clin. Exp. Rheumatol. 17(5):521–526.PubMed
11.
Zurück zum Zitat Shanley, T. P., J. L. Foreback, D. G. Remick, T. R. Ulich, S. L. Kunkel, and P. A. Ward. 1997. Regulatory effects of interleukin-6 in immunoglobulin G immune complex-induced lung injury. Am. J. Pathol. 151(1):193–203.PubMed Shanley, T. P., J. L. Foreback, D. G. Remick, T. R. Ulich, S. L. Kunkel, and P. A. Ward. 1997. Regulatory effects of interleukin-6 in immunoglobulin G immune complex-induced lung injury. Am. J. Pathol. 151(1):193–203.PubMed
12.
Zurück zum Zitat Morrow, J. D., and M. R. Opp. 2005. Diurnal variation of lipopolysaccharide-induced alterations in sleep and body temperature of interleukin-6-deficient mice. Brain Behav. Immun. 19(1):40–51.PubMedCrossRef Morrow, J. D., and M. R. Opp. 2005. Diurnal variation of lipopolysaccharide-induced alterations in sleep and body temperature of interleukin-6-deficient mice. Brain Behav. Immun. 19(1):40–51.PubMedCrossRef
13.
Zurück zum Zitat Johnson, K. J., and P. A. Ward. 1974. Acute immunologic pulmonary alveolitis. J. Clin. Invest. 54(2):349–357.PubMedCrossRef Johnson, K. J., and P. A. Ward. 1974. Acute immunologic pulmonary alveolitis. J. Clin. Invest. 54(2):349–357.PubMedCrossRef
14.
Zurück zum Zitat Ward, P. A. 1965. Cochrane CG. Bound complement and immunologic injury of blood vessels. J. Exp. Med. 121:215–234.PubMedCrossRef Ward, P. A. 1965. Cochrane CG. Bound complement and immunologic injury of blood vessels. J. Exp. Med. 121:215–234.PubMedCrossRef
15.
Zurück zum Zitat Ward, P. A., J. S. Warren, and K. J. Johnson. 1988. Leukocytes, oxidants and tissue injury. Perspect. Crit. Care 1:69–81. Ward, P. A., J. S. Warren, and K. J. Johnson. 1988. Leukocytes, oxidants and tissue injury. Perspect. Crit. Care 1:69–81.
16.
Zurück zum Zitat Warren, J. S., K. J. Johnson, and P. A. Ward. 1991. Immunoglobulin and complement mediated immune injury. In: The lung: scientific foundations, R. J. Crystal, J. B. West, P. J. Barnes, N. S. Cherniack and E. R. Weibel eds. Raven, New York, pp. 1939–1949. Warren, J. S., K. J. Johnson, and P. A. Ward. 1991. Immunoglobulin and complement mediated immune injury. In: The lung: scientific foundations, R. J. Crystal, J. B. West, P. J. Barnes, N. S. Cherniack and E. R. Weibel eds. Raven, New York, pp. 1939–1949.
17.
Zurück zum Zitat Guo, R. F., and P. A. Ward. 2005. Role of C5a in inflammatory responses. Review. Ann. Rev. Immunol. 23:821–852.CrossRef Guo, R. F., and P. A. Ward. 2005. Role of C5a in inflammatory responses. Review. Ann. Rev. Immunol. 23:821–852.CrossRef
18.
Zurück zum Zitat Warner, R. L., C. S. Lewis, L. Beltran, E. M. Younkin, J. Varani, and K. J. Johnson. 2001. Role of stromelysin 1 and gelatinase B in experimental acute lung injury. Am. J. Respir. Cell Mol. Biol. 24 (5):537–544.PubMed Warner, R. L., C. S. Lewis, L. Beltran, E. M. Younkin, J. Varani, and K. J. Johnson. 2001. Role of stromelysin 1 and gelatinase B in experimental acute lung injury. Am. J. Respir. Cell Mol. Biol. 24 (5):537–544.PubMed
19.
Zurück zum Zitat Warren, J. S. 1991. Disparate roles for TNF in the pathogenesis of acute immune complex alveolitis and dermal vasculitis. Clin. Immunol. Immunopathol. 61(2 Pt 1):249–259.PubMed Warren, J. S. 1991. Disparate roles for TNF in the pathogenesis of acute immune complex alveolitis and dermal vasculitis. Clin. Immunol. Immunopathol. 61(2 Pt 1):249–259.PubMed
20.
Zurück zum Zitat Speyer, C. L., N. J. Rancilio, S. D. McClintock, J. D.Crawford, H. Gao, J. V. Sarma, and P. A. Ward. 2005. Regulatory effects of estrogen on acute lung inflammation in mice. Am. J. Physiol. Cell Physiol. 288(4):C881–C890.PubMedCrossRef Speyer, C. L., N. J. Rancilio, S. D. McClintock, J. D.Crawford, H. Gao, J. V. Sarma, and P. A. Ward. 2005. Regulatory effects of estrogen on acute lung inflammation in mice. Am. J. Physiol. Cell Physiol. 288(4):C881–C890.PubMedCrossRef
21.
Zurück zum Zitat Riedemann, N. C., T. A. Neff, R. F. Guo, K. D. Bernacki, I. J. Laudes, J. V. Sarma, J. D. Lambris, and P. A. Ward. 2003. Protective effects of IL-6 blockade in sepsis are linked to reduced C5a receptor expression. J. Immunol. 170(1):503–507.PubMed Riedemann, N. C., T. A. Neff, R. F. Guo, K. D. Bernacki, I. J. Laudes, J. V. Sarma, J. D. Lambris, and P. A. Ward. 2003. Protective effects of IL-6 blockade in sepsis are linked to reduced C5a receptor expression. J. Immunol. 170(1):503–507.PubMed
22.
Zurück zum Zitat Gennari, R., and J. W. Alexander. 1995. Anti-interleukin-6 antibody treatment improves survival during gut-derived sepsis in a time-dependent manner by enhancing host defense. Crit. Care Med. 23(12):1945–1953.PubMedCrossRef Gennari, R., and J. W. Alexander. 1995. Anti-interleukin-6 antibody treatment improves survival during gut-derived sepsis in a time-dependent manner by enhancing host defense. Crit. Care Med. 23(12):1945–1953.PubMedCrossRef
23.
Zurück zum Zitat Remick, D. G., G. Bolgos, S. Copeland, and J. Siddiqui. 2005. Role of interleukin-6 in mortality from and physiologic responses to sepsis. Infect. Immun. 73(5):2751–2757.PubMedCrossRef Remick, D. G., G. Bolgos, S. Copeland, and J. Siddiqui. 2005. Role of interleukin-6 in mortality from and physiologic responses to sepsis. Infect. Immun. 73(5):2751–2757.PubMedCrossRef
24.
Zurück zum Zitat Kluger, M. J., W. Kozak, L. R. Leon, and C. A. Conn. 1998. The use of knockout mice to understand the role of cytokines in fever. Clin. Exp. Pharmacol. Physiol. 25(2):141–144.PubMed Kluger, M. J., W. Kozak, L. R. Leon, and C. A. Conn. 1998. The use of knockout mice to understand the role of cytokines in fever. Clin. Exp. Pharmacol. Physiol. 25(2):141–144.PubMed
25.
Zurück zum Zitat Sundgren-Andersson, A. K., P. Ostlund, and T. Bartfai. 1996. IL-6 is essential in TNFα induced fever. Am. J. Physiol. 275: R2028–R2034. Sundgren-Andersson, A. K., P. Ostlund, and T. Bartfai. 1996. IL-6 is essential in TNFα induced fever. Am. J. Physiol. 275: R2028–R2034.
26.
Zurück zum Zitat Johnston, R. A., I. N. Schwartzman, L. Flynt, and S. A. Shore. 2005. Role of interleukin-6 in murine airway responses to ozone. Am. J. Physiol. Lung Cell Mol. Physiol. 288(2):L390-L397.PubMedCrossRef Johnston, R. A., I. N. Schwartzman, L. Flynt, and S. A. Shore. 2005. Role of interleukin-6 in murine airway responses to ozone. Am. J. Physiol. Lung Cell Mol. Physiol. 288(2):L390-L397.PubMedCrossRef
27.
Zurück zum Zitat Akira, S., H. Isshiki, T. Nakajima, S. Kinoshita, Y. Nishio, S. Natsuka, and T. Kishimoto. 1992. Regulation of expression of the interleukin 6 gene: structure and function of the transcription factor NF-IL6. Ciba Found Symp. 167:47–62.PubMed Akira, S., H. Isshiki, T. Nakajima, S. Kinoshita, Y. Nishio, S. Natsuka, and T. Kishimoto. 1992. Regulation of expression of the interleukin 6 gene: structure and function of the transcription factor NF-IL6. Ciba Found Symp. 167:47–62.PubMed
28.
Zurück zum Zitat Kopf, M., G. Le Gros, A. J. Coyle, M. Kosco-Vilbois, and F. Brombacher. 1995. Immune responses of IL-4, IL-5, IL-6 deficient mice. Immunol. Rev. 148:45–69.PubMedCrossRef Kopf, M., G. Le Gros, A. J. Coyle, M. Kosco-Vilbois, and F. Brombacher. 1995. Immune responses of IL-4, IL-5, IL-6 deficient mice. Immunol. Rev. 148:45–69.PubMedCrossRef
29.
Zurück zum Zitat Tackey, E., P. E. Lipsky, and G. G. Illei. 2004. Rationale for interleukin-6 blockade in systemic lupus erythematosus. Lupus. 13(5):339–343.PubMedCrossRef Tackey, E., P. E. Lipsky, and G. G. Illei. 2004. Rationale for interleukin-6 blockade in systemic lupus erythematosus. Lupus. 13(5):339–343.PubMedCrossRef
30.
Zurück zum Zitat Choy, E. 2004. Clinical experience with inhibition of interleukin-6. Rheum. Dis. Clin. North Am. 30(2):405–415.PubMedCrossRef Choy, E. 2004. Clinical experience with inhibition of interleukin-6. Rheum. Dis. Clin. North Am. 30(2):405–415.PubMedCrossRef
31.
Zurück zum Zitat Peterson, A. M., and B. K. Pedersen. 2005. The anti-inflammatory effect of exercise. Review. J. Appl. Physiol. 98(4):1154–1162.CrossRef Peterson, A. M., and B. K. Pedersen. 2005. The anti-inflammatory effect of exercise. Review. J. Appl. Physiol. 98(4):1154–1162.CrossRef
32.
Zurück zum Zitat Gerlai, R., S. P. Williams, B. Cairns, N. Van Bruggen, P. Moran, A. Shih, I. Caras, H. Sauer, H. S. Phillips, and J. W. Winslow. 1998. Protein targeting in the analysis of learning and memory: a potential alternative to gene targeting. Exp. Brain Res. 123(1–2):24–35.PubMedCrossRef Gerlai, R., S. P. Williams, B. Cairns, N. Van Bruggen, P. Moran, A. Shih, I. Caras, H. Sauer, H. S. Phillips, and J. W. Winslow. 1998. Protein targeting in the analysis of learning and memory: a potential alternative to gene targeting. Exp. Brain Res. 123(1–2):24–35.PubMedCrossRef
33.
34.
Zurück zum Zitat Gerlai, R. 2001. Gene targeting: technical confounds and potential solutions in behavioral brain research. Behav. Brain Res. 125(1–2):13–21.PubMedCrossRef Gerlai, R. 2001. Gene targeting: technical confounds and potential solutions in behavioral brain research. Behav. Brain Res. 125(1–2):13–21.PubMedCrossRef
Metadaten
Titel
Role of Interleukin-6 in Immune Complex Induced Models of Vascular Injury
verfasst von
Shannon D. McClintock
Adam G. Barron
Eric W. Olle
Michael P. Deogracias
Roscoe L. Warner
Mark Opp
Kent J. Johnson
Publikationsdatum
01.12.2005
Erschienen in
Inflammation / Ausgabe 4-6/2005
Print ISSN: 0360-3997
Elektronische ISSN: 1573-2576
DOI
https://doi.org/10.1007/s10753-006-9011-1

Weitere Artikel der Ausgabe 4-6/2005

Inflammation 4-6/2005 Zur Ausgabe

Leitlinien kompakt für die Innere Medizin

Mit medbee Pocketcards sicher entscheiden.

Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag

Reizdarmsyndrom: Diäten wirksamer als Medikamente

29.04.2024 Reizdarmsyndrom Nachrichten

Bei Reizdarmsyndrom scheinen Diäten, wie etwa die FODMAP-arme oder die kohlenhydratreduzierte Ernährung, effektiver als eine medikamentöse Therapie zu sein. Das hat eine Studie aus Schweden ergeben, die die drei Therapieoptionen im direkten Vergleich analysierte.

Notfall-TEP der Hüfte ist auch bei 90-Jährigen machbar

26.04.2024 Hüft-TEP Nachrichten

Ob bei einer Notfalloperation nach Schenkelhalsfraktur eine Hemiarthroplastik oder eine totale Endoprothese (TEP) eingebaut wird, sollte nicht allein vom Alter der Patientinnen und Patienten abhängen. Auch über 90-Jährige können von der TEP profitieren.

Niedriger diastolischer Blutdruck erhöht Risiko für schwere kardiovaskuläre Komplikationen

25.04.2024 Hypotonie Nachrichten

Wenn unter einer medikamentösen Hochdrucktherapie der diastolische Blutdruck in den Keller geht, steigt das Risiko für schwere kardiovaskuläre Ereignisse: Darauf deutet eine Sekundäranalyse der SPRINT-Studie hin.

Bei schweren Reaktionen auf Insektenstiche empfiehlt sich eine spezifische Immuntherapie

Insektenstiche sind bei Erwachsenen die häufigsten Auslöser einer Anaphylaxie. Einen wirksamen Schutz vor schweren anaphylaktischen Reaktionen bietet die allergenspezifische Immuntherapie. Jedoch kommt sie noch viel zu selten zum Einsatz.

Update Innere Medizin

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.