STAPHLOCOCCUS AUREUS İLE OLUŞTURULAN DENEYSEL İNTRAABDOMİNAL KAYNAKLI BAKTERİYEMİ MODELİNDE BETA GLUKANIN İMMÜNOMODULATÖR ETKİSİNİN ARAŞTIRILMASI
Öz
AMAÇ: Bu çalışmanın amacı S. aureus ile oluşturulan deneysel intraabdominal kaynaklı bakteriyemi modelinde beta glukanın immünomodulatör etkisini araştırmaktır.
GEREÇ VE YÖNTEM: Wistar albina sıçanlardan 30’u rastgele 4 gruba ayrıldı. Sırasıyla Staphylococcus aureus bakteriyemisi (SAB), sefazolin ile tedavi, beta glukan tedavi, beta glukan ve sefazolin tedavi grupları oluşturuldu. İntraabdominal yolla verilen 12x10 8 cfu/ml 1 cc S. aureus verildikten sonra intraabdominal 4 mg/kg beta glukan ve 100 mg/kg sefazolin verildi. 2 saat sonra 0,5 cc kan alınarak kan kültür şişesine ekim yapıldı. 4-6-8. saat sonra Tümör nekroz faktörü alfa (TNF-α), İnterlökin-1( IL-1), İnterlökin-6 (IL-6), İnterferon gama (IFN-γ) düzeyleri araştırıldı.
BULGULAR: Biyokimyasal analizlere göre; çalışma sonunda beta glukan 6. saatte IFN-γ’yı arttırdığı, ancak 4. ve 8. saatlerde arttırmadığı görüldü. Sefazolin ile birlikte verildiğinde 6. saatte bu artış daha belirgin olmaktadır. Ancak sefazolin verilen grupta IFN-γ değerleri beta glukandan daha yüksek düzeyde saptandı. Serum TNF-α düzeyleri değerlendirildiğinde, beta glukan verilen grupta 8. saatte TNF-α düzeyinde bir baskılanma saptansa da SAB grubundan daha yüksek olarak bulundu. Serum IL-1 düzeyleri değerlendirildiğinde, beta glukan verilen grupta 4-6 ve 8. saatlerde IL-1 düzeyleri SAB grubuna göre daha yüksekti. Beta glukana sefazolin eklenen grupta 8. saatte IL-1 düzeylerinde azalma tesbit edildiyse de, bu düzeyler SAB grubundan yüksek saptandı. Serum IL-6 seviyesi değerlendirildiğinde, beta glukan verilen grupta SAB grubuna göre ilk 8 saatte IL-6 salınımında artış saptandı. Beta glukan sefazolinle birlikte uygulandığında ise IL-6 artışının ilk 8. saatte en yüksek düzeye ulaştığı görüldü.
SONUÇ: Bu deneysel intraabdominal kaynaklı bakteriyemi modeli beta glukanın özellikle ilk saatlerde TNF-α, IL-1 üretimini baskılamadığını, IL-6, IFN-γ salınımını arttırdığını göstermiştir. Bu sonuçlara göre deneysel intraabdominal kaynaklı bakteriyemi tedavisinde beta glukan kullanımının yararı konusunda anlamlı bilgilere ulaşılamadı.
Anahtar Kelimeler
Destekleyen Kurum
Afyonkocatepe üniversitesi tıp fakültesi BAP
Proje Numarası
08.TIP.14
Kaynakça
- 1. Gudiol C, Cuervo G, Shaw E, Pujol M, Carratala J. Pharmacotherapeutic options for treating Staphylococcus aureus bacteremia. Expert Opin Pharmacother. 2017;18(18):1947-63.
- 2. Heyland DK, Hopman W, Coo H, Tranmer J. McColl MA. Long-term health-related quality of life in survivors of sepsis. Short Form 36: A valid and reliable measure of health- related quality of life. Crit Care Med. 2000;28:3599–605.
- 3. Holub M, Kluckuva Z, Beneda B. Changes in lymphocytes subpopulations and CD3/DR expression in sepsis. Clin Microbiol Infect. 2000;6:657-60.
- 4. Tsiotou AG, Sakorafas GH, Anagnostopoulos G, Bramis J. Septic shock; current pathogenetic concepts from a clinical perspective. Med Sci Monit. 2005;11:76-5.
- 5. Carrow DJ. Beta-1,3-Glucan as a primary immune activator. Townsend Letter. 1996:6;84-91.
- 6. Mohagheghur N, Dawson M, Hobbs P, et al. Glucans as immunological adjuvants. Adv Exp Med Biol. 1995;383:13-2.
- 7. Sherwood ER, Varma TK, Fram RY, Lın CY, Koutrouvelıs AP, Tolıver-Kınsky TE. Glucan phosphate potentiates endotoxininduced interferon-γ expression in immunocompetent mice, but attenuates induction of endotoxin tolerance. Clinical Science. 2001;101:541–50.
- 8. Russell JA. Management of sepsis. N Engl J Med. 2006;355:1699-713.
- 9. Abraham E (Editors). Mechanisms of Sepsis-Induced Organ Dysfunction and Recovery of the series. In: Texereau JV, Lemiale J, Mira P. Genetics and Severe Sepsis. Update in Intensive Care and Emergency Medicine. 2007;43, 17-33.
- 10. Song M, Kellum JA. Interleukin-6. Crit Care Med. 2005;33,463-5.
- 11. Kellum JA, Kong L, Fink MP, et al. Understanding the inflammatory cytokine response in pneumonia and sepsis: results of the Genetic and Inflammatory Markers of Sepsis (GenIMS) Study. Arch Intern Med. 2007;167(15),1655-63.
- 12. Prucha M, Bellingan G, Zazula R. Sepsis biomarkers. Clin Chim Acta. 2015;440,(2),97-103.
- 13. Breivik T, Opstad PK, Engstad R, Gundersen G, Gjermo P, Preus H. Soluble Beta-1,3/ 1,6-glucan from yeast inhibits experimental periodontal disease in Wistar rats. J Clin Periodontal. 2005;32:347-52.
- 14. Yun CH, Estrada A, Van Kessel A, Park BC, Laarveld B. Beta –glucan, extracted from oat, enhances disease resistance against bacterial and parasitic infections. FEMS Immunol and Med Microbiol. 2003;35:67-5.
- 15. Brown GD, Gordon S. Fungal β–Glucans and Mammalian Immunity. Immunity. 2003;19:311–5.
- 16. Kubala L, Ruzickova J, Nickova K, Sandula J, Ciz M, Lojek A. The effect of (1-3 ) –beta- D- glucans, carboxymethylglucan and schizophyllan on human leukocytes in vitro. Carbohydr Res. 2003;338:2835-40.
- 17. Xiao Z, Trincado CA, Murtaugh MP. β-glucan enhancement of T cell INFγ response in swine. Vet Immunol Immunopathol. 2004;102:315-20.
- 18. Soltys J, Quinn MT. Modulation of endotoxin- and enterotoxininduced cytokine release by in vivo treatment with beta-(1,6)-branched beta-(1,3)- glucan. Infect Immun. 1999;67:244–52.
- 19. Sener G, Toklu H, Ercan F, Erkani G. Protective effect of beta glucan against oxidative organ injury in a rat model of sepsis. Int Immunopharmacol. 2005;5:1387-96.
- 20. Toklu HZ, Sener G, Jahovic N, Uslu B, Arbak S, Yegen BC. Beta glucan protects against burn-induced oxidative organ damage in rats. Int Immunopharmacol. 2006;6: 156– 69.
- 21. Bedirli A, Kerem M, Pasaoglu H, et al. Beta-glucan attenuates inflammatory cytokine release and prevents acute lung ınjury ın an experımental model of sepsıs. Shock. 2007;27:397-401.
- 22. Peters K, Unger RE, Brunger J, Kirkpatrick CJ. Molecular basis of endothelial dysfunction in sepsis. Cardiovascular Research. 2003;60:49- 57.
- 23. Sandvik A, Wang YY, Morton HC, Aasen AO, Wang JE, Johansen FE. Oral and systemic administration of beta-glucan protects against lipopolysaccharide-induced shock and injury in rats. Clinical and Experimental Immunology. 2007;148:168-77.
- 24. Wakshull E, Brunke-Reese D, Lindermuth J, et al. PGG-glucan, a soluble [beta]-(1,3)-glucan, enhances the oxidative burst response, microbicidal activity, and activates an NF-[kappa]B-like factor in human PMN. Evidence for a glycosphingolipid [beta]-(1,3)-glucan receptor. Immunopharmacology. 1999;41:89–107.
- 25. Lyuksutova OI, Murphey ED, Toliver-Kinsky TE, et al. Glucan phosphate treatment attenuates burninduced inflammation and improves resistance to Pseudomonas aeruginosa burn wound infection. Shock. 2005;23:224-32.
- 26. Iraz M, Iraz M, Esrefoglu M, Aydın MS. Protective effect of β-glucan on acute lung injury induced by lipopolysaccharide in rats. Turk J Med Sci. 2015;45:261-7.
- 27. Engstad CS, Engstad RE, Olsen JO, Osterud B. The effect of soluble beta1,3-glucan and lipopolysaccharide on cytokine production and coagulation activation in whole blood. Int Immunopharmacol. 2002;2:1585–97.
- 28. Babayiğit H, Kucuk C, Sozuer E, Yazici C, Kose K, Akgun H. Protective effect of beta-glucan on lung ingury after cecal ligation and puncture in rats. Intensive Care Med. 2005;31:865-70.
INVESTIGATION OF THE IMMUNOMODULATOR EFFECT OF BETA GLUCAN IN THE EXPERIMENTAL INTRAABDOMINAL BACTERIEMIA MODEL WITH STAPHYLOCOCCUS AUREUS
Öz
OBJECTIVE: The purpose of this study is to investigate the immunomodulatory effect of beta glucan in an experimental model of intraabdominal bacteremia induced by S. aureus.
MATERIAL AND METHODS: Thirty Wistar albino rats were randomly divided into four groups. Staphylococcus aureus bacteremia (SAB), treatment with cefazolin, treatment with beta glucan, treatment with both cefazolin and beta glucan groups were constituted respectively. 4 mg/kg beta glucan and 100 mg/kg cefazolin were given after 12x10 8 cfu/ml 1 cc S. aureus was given intraabdominally. After two hours, 0.5 cc blood was drawn and put into blood culture bottles. Levels of Tumor necrosis factor-alpha (TNF-α), interleukin-1 (IL-1), interleukin-6 (IL-6), and Interferon gamma (IFN-γ) were evaluated after 4th, 6th and 8th hours.
RESULTS: According to the biochemical analyses; At the end of the study it was seen that beta glucan increased the level of IFN-γ at 6th hour, but did not at 4th and 8th hours. This increase became more apparent at 6 th hour when it was given with cefazolin. However IFN-γ levels were found to be higher in the group which cefazolin was given than beta glucan was. As the level of serum TNF-α was evaluated, although there was a supression at 8th hour, it was found to be higher in the group which beta glucan was given than the SAB group. Serum IL-1 levels were higher at 4th, 6th and 8th hours in the group beta glucan was given than the SAB group. Although a decline in IL-1 level was detected in the group which cefazolin was added to beta glucan at 8th hour, this level was found to be higher than the SAB group. When the serum IL-6 level was evaluated, an increase in release of IL-6 was found in the group beta glucan was given in the first 8 hours when it was compared with SAB group. When beta glucan was given with cefazolin, it was observed that IL-6 increased to the highest level at 8th hour.
CONCLUSIONS: This experimental intra-abdominal bacteremia model, demonstrated that beta glucan did not supress the production of TNF-α and IL-1, and increased the release of IL- 6 and IFN-γ, especially in the first hours. According to these results, no significant knowledge could be obtained about the benefit of using beta glucan in the treatment of experimental model of intraabdominal bacteremia.
Anahtar Kelimeler
Proje Numarası
08.TIP.14
Kaynakça
- 1. Gudiol C, Cuervo G, Shaw E, Pujol M, Carratala J. Pharmacotherapeutic options for treating Staphylococcus aureus bacteremia. Expert Opin Pharmacother. 2017;18(18):1947-63.
- 2. Heyland DK, Hopman W, Coo H, Tranmer J. McColl MA. Long-term health-related quality of life in survivors of sepsis. Short Form 36: A valid and reliable measure of health- related quality of life. Crit Care Med. 2000;28:3599–605.
- 3. Holub M, Kluckuva Z, Beneda B. Changes in lymphocytes subpopulations and CD3/DR expression in sepsis. Clin Microbiol Infect. 2000;6:657-60.
- 4. Tsiotou AG, Sakorafas GH, Anagnostopoulos G, Bramis J. Septic shock; current pathogenetic concepts from a clinical perspective. Med Sci Monit. 2005;11:76-5.
- 5. Carrow DJ. Beta-1,3-Glucan as a primary immune activator. Townsend Letter. 1996:6;84-91.
- 6. Mohagheghur N, Dawson M, Hobbs P, et al. Glucans as immunological adjuvants. Adv Exp Med Biol. 1995;383:13-2.
- 7. Sherwood ER, Varma TK, Fram RY, Lın CY, Koutrouvelıs AP, Tolıver-Kınsky TE. Glucan phosphate potentiates endotoxininduced interferon-γ expression in immunocompetent mice, but attenuates induction of endotoxin tolerance. Clinical Science. 2001;101:541–50.
- 8. Russell JA. Management of sepsis. N Engl J Med. 2006;355:1699-713.
- 9. Abraham E (Editors). Mechanisms of Sepsis-Induced Organ Dysfunction and Recovery of the series. In: Texereau JV, Lemiale J, Mira P. Genetics and Severe Sepsis. Update in Intensive Care and Emergency Medicine. 2007;43, 17-33.
- 10. Song M, Kellum JA. Interleukin-6. Crit Care Med. 2005;33,463-5.
- 11. Kellum JA, Kong L, Fink MP, et al. Understanding the inflammatory cytokine response in pneumonia and sepsis: results of the Genetic and Inflammatory Markers of Sepsis (GenIMS) Study. Arch Intern Med. 2007;167(15),1655-63.
- 12. Prucha M, Bellingan G, Zazula R. Sepsis biomarkers. Clin Chim Acta. 2015;440,(2),97-103.
- 13. Breivik T, Opstad PK, Engstad R, Gundersen G, Gjermo P, Preus H. Soluble Beta-1,3/ 1,6-glucan from yeast inhibits experimental periodontal disease in Wistar rats. J Clin Periodontal. 2005;32:347-52.
- 14. Yun CH, Estrada A, Van Kessel A, Park BC, Laarveld B. Beta –glucan, extracted from oat, enhances disease resistance against bacterial and parasitic infections. FEMS Immunol and Med Microbiol. 2003;35:67-5.
- 15. Brown GD, Gordon S. Fungal β–Glucans and Mammalian Immunity. Immunity. 2003;19:311–5.
- 16. Kubala L, Ruzickova J, Nickova K, Sandula J, Ciz M, Lojek A. The effect of (1-3 ) –beta- D- glucans, carboxymethylglucan and schizophyllan on human leukocytes in vitro. Carbohydr Res. 2003;338:2835-40.
- 17. Xiao Z, Trincado CA, Murtaugh MP. β-glucan enhancement of T cell INFγ response in swine. Vet Immunol Immunopathol. 2004;102:315-20.
- 18. Soltys J, Quinn MT. Modulation of endotoxin- and enterotoxininduced cytokine release by in vivo treatment with beta-(1,6)-branched beta-(1,3)- glucan. Infect Immun. 1999;67:244–52.
- 19. Sener G, Toklu H, Ercan F, Erkani G. Protective effect of beta glucan against oxidative organ injury in a rat model of sepsis. Int Immunopharmacol. 2005;5:1387-96.
- 20. Toklu HZ, Sener G, Jahovic N, Uslu B, Arbak S, Yegen BC. Beta glucan protects against burn-induced oxidative organ damage in rats. Int Immunopharmacol. 2006;6: 156– 69.
- 21. Bedirli A, Kerem M, Pasaoglu H, et al. Beta-glucan attenuates inflammatory cytokine release and prevents acute lung ınjury ın an experımental model of sepsıs. Shock. 2007;27:397-401.
- 22. Peters K, Unger RE, Brunger J, Kirkpatrick CJ. Molecular basis of endothelial dysfunction in sepsis. Cardiovascular Research. 2003;60:49- 57.
- 23. Sandvik A, Wang YY, Morton HC, Aasen AO, Wang JE, Johansen FE. Oral and systemic administration of beta-glucan protects against lipopolysaccharide-induced shock and injury in rats. Clinical and Experimental Immunology. 2007;148:168-77.
- 24. Wakshull E, Brunke-Reese D, Lindermuth J, et al. PGG-glucan, a soluble [beta]-(1,3)-glucan, enhances the oxidative burst response, microbicidal activity, and activates an NF-[kappa]B-like factor in human PMN. Evidence for a glycosphingolipid [beta]-(1,3)-glucan receptor. Immunopharmacology. 1999;41:89–107.
- 25. Lyuksutova OI, Murphey ED, Toliver-Kinsky TE, et al. Glucan phosphate treatment attenuates burninduced inflammation and improves resistance to Pseudomonas aeruginosa burn wound infection. Shock. 2005;23:224-32.
- 26. Iraz M, Iraz M, Esrefoglu M, Aydın MS. Protective effect of β-glucan on acute lung injury induced by lipopolysaccharide in rats. Turk J Med Sci. 2015;45:261-7.
- 27. Engstad CS, Engstad RE, Olsen JO, Osterud B. The effect of soluble beta1,3-glucan and lipopolysaccharide on cytokine production and coagulation activation in whole blood. Int Immunopharmacol. 2002;2:1585–97.
- 28. Babayiğit H, Kucuk C, Sozuer E, Yazici C, Kose K, Akgun H. Protective effect of beta-glucan on lung ingury after cecal ligation and puncture in rats. Intensive Care Med. 2005;31:865-70.
Ayrıntılar
| Birincil Dil | İngilizce |
|---|---|
| Konular | Klinik Tıp Bilimleri |
| Bölüm | Makaleler-Araştırma Yazıları |
| Yazarlar | |
| Proje Numarası | 08.TIP.14 |
| Yayımlanma Tarihi | 17 Ocak 2022 |
| Kabul Tarihi | 26 Mayıs 2021 |
| Yayımlandığı Sayı | Yıl 2022 Cilt: 23 Sayı: 1 |
Kaynak Göster
