Ukr.Biochem.J. 2019; Volume 91, Issue 5, Sep-Oct, pp. 7-15
doi: https://doi.org/10.15407/ubj91.05.007
Effect of recombinant human interleukin-7 on Pseudomonas aeruginosa wound infection
S. M. Grigorieva1, D. B. Starosyla1, S. L. Rybalko1,
V. V. Motronenko2, T. M. Lutsenko2,3, O. Yu. Galkin2
1Gromashevsky Institute of Epidemiology and Infectious Diseases,
National Academy of Medical Sciences of Ukraine, Kyiv;
2National Technical University of Ukraine “Igor Sikorsky Kyiv Polytechnic Institute”;
3UA Pro-Pharma LLC, Kyiv, Ukraine;
e-mail: alexfbt@gmail.com
Received: 01 July 2019; Accepted: 13 August 2019
A wide range of interleukin-7 (IL-7) biological effects suggests that application of appropriate preparations in clinical practice will stimulate immunity in patients with lymphocytic exhaustion or autoimmune diseases. Studies are being conducted for IL-7 based preparations aimed at restoration of the immune system of patients with immunodeficiency of different origins. Pseudomonas aeruginosa is an important pathogen, which causes nosocomial infections in hospitalized patients. Infection factors, affecting the immune status of the host, play a key role. A promising and relevant scientific endeavor is the study of the effect of recombinant IL-7 (rIL-7) as an adjunct therapy in wound infections caused by P. aeruginosa. The aim of this study was to evaluate the effectiveness of rIL-7 use in P. aeruginosa wound infection in mice. The experiments were conducted using a standardized rIL-7 preparation, P. aeruginosa strain and 20 white non-inbred mice. The preparation of rIL-7 after all stages of purification was characterized by the content of ballast proteins and impurities via electrophoresis in a polyacrylamide gel in reducing conditions, and its biological activity was evaluated in the MTT test by means of proliferation of peripheral blood mononuclear cells. In the mice, the fur was removed, the neck nape was intentionally injured and P. aeruginosa bacteria were injected into the wound of each animal (0.1 ml of suspension with a bacterial cell concentration of 0.08×109 cells/ml). Starting from the 2nd day, bacterial examination of the wound material was carried out daily. Starting from the 3rd day, the mice (experimental group, n = 10) were intraperitoneally administered 5 μg (0.1 ml) of the rIL-7 preparation. In the control group of animals (n = 10), the rIL-7 preparation was not administered. In 80% of experimental animals (administered the rIL-7 preparation), the healing of wounds and elimination of the pathogen of purulent inflammatory infection P. aeruginosa occurred on the 7th day. On the 9th day from the beginning of wound infection, wound healing and elimination of P. aeruginosa occurred in all experimental mice. In 60% of mice from the control group (did not receive treatment with rIL-7), wound healing and the elimination of P. aeruginosa occurred on the 9th day. Wound healing and elimination of P. aeruginosa in all mice of the control group occurred on the 14th day. Thus, in mice treated with rIL-7, wound healing and elimination of the pathogen occurred 5 days earlier than in mice from the control group (without rIL-7 treatment). Subsequent studies may be aimed at developing protocols for the treatment of wound infections using an rIL-7 preparation in patients with a compromised immune system Therefore, rIL-7 is a promising preparation for the treatment of complex wound infections.
Keywords: Pseudomonas aeruginosa, recombinant human interleukin-7, therapy, wound infection
References:
- Slyvka AV, Okunev OV. Molecular mechanisms of versatile biological activity of interleukin-7. Biopolym Cell. 2014;30(5):349-357. CrossRef
- Galkin OYu, Lutsenko TM, Gorshunov YuV, Motronenko VV. Development of the method for microbiological purity testing of recombinant human interleukin-7-based product. Ukr Biochem J. 2017;89(3):52-59. CrossRef
- Lundström W, Fewkes NM, Mackall CL. IL-7 in human health and disease. Semin Immunol. 2012 Jun;24(3):218-24. PubMed, PubMedCentral, CrossRef
- Dawood A, Abdul Basit S, Jayaraj M, Gish RG. Drugs in Development for Hepatitis B. Drugs. 2017 Aug;77(12):1263-1280. PubMed, PubMedCentral, CrossRef
- Shindo Y, Fuchs AG, Davis CG, Eitas T, Unsinger J, Burnham CD, Green JM, Morre M, Bochicchio GV, Hotchkiss RS. Interleukin 7 immunotherapy improves host immunity and survival in a two-hit model of Pseudomonas aeruginosa pneumonia. J Leukoc Biol. 2017 Feb;101(2):543-554. PubMed, PubMedCentral, CrossRef
- Teng D, Ding L, Cai B, Luo Q, Wang H. Interleukin-7 enhances anti-tumor activity of CD8+ T cells in patients with hepatocellular carcinoma. Cytokine. 2019;118:115-123. PubMed, CrossRef
- Chornopyshhuk RI. Local immunocorrection in the complex treatment of infected wounds: a monograph. Vinnycya, 2017. 210 p. (In Ukrainian).
- Kovalchuk LB, Gankovskaya LV, Levchenko VA. Immunocorrection with cytokines. Bull Russ State Med Univ. 2002;3:6-12. (In Russian).
- Lee AC, Jones AL. Multi-resistant Pseudomonas aeruginosa ST235 in cystic fibrosis. Paediatr Respir Rev. 2018 Jun;27:18-20. PubMed, CrossRef
- Lim SZP, Fitzgerald DA. Treating resistant Pseudomonas aeruginosa lung disease in young children with cystic fibrosis. Paediatr Respir Rev. 2018 Jun;27:33-36. PubMed, CrossRef
- Estaji M, Tabasi M, Sadeghpour Heravi F, Kheirvari Khezerloo J, Radmanesh A, Raheb J, Ghadirzadeh MR, Tabatabaei A. Genotypic identification of Pseudomonas aeruginosa strains isolated from patients with urinary tract infection. Comp Immunol Microbiol Infect Dis. 2019 Aug;65:23-28. PubMed, CrossRef
- Sharif M, Wong CHM, Harky A. Sternal Wound Infections, Risk Factors and Management – How Far Are We? A Literature Review. Heart Lung Circ. 2019 Jun;28(6):835-843. PubMed, CrossRef
- Cefalu JE, Barrier KM, Davis AH. Wound Infections in Critical Care. Crit Care Nurs Clin North Am. 2017 Mar;29(1):81-96. PubMed, CrossRef
- Dou Y, Huan J, Guo F, Zhou Z, Shi Y. Pseudomonas aeruginosa prevalence, antibiotic resistance and antimicrobial use in Chinese burn wards from 2007 to 2014. J Int Med Res. 2017 Jun;45(3):1124-1137. PubMed, PubMed, CrossRef
- Decraene V, Ghebrehewet S, Dardamissis E, Huyton R, Mortimer K, Wilkinson D, Shokrollahi K, Singleton S, Patel B, Turton J, Hoffman P, Puleston R. An outbreak of multidrug-resistant Pseudomonas aeruginosa in a burns service in the North of England: challenges of infection prevention and control in a complex setting. J Hosp Infect. 2018 Dec;100(4):e239-e245. PubMed, CrossRef
- Nichols DP, Caceres S, Caverly L, Fratelli C, Kim SH, Malcolm K, Poch KR, Saavedra M, Solomon G, Taylor-Cousar J, Moskowitz S, Nick JA. Effects of azithromycin in Pseudomonas aeruginosa burn wound infection. J Surg Res. 2013 Aug;183(2):767-76. PubMed, PubMedCentral, CrossRef
- Pang Z, Raudonis R, Glick BR, Lin TJ, Cheng Z. Antibiotic resistance in Pseudomonas aeruginosa: mechanisms and alternative therapeutic strategies. Biotechnol Adv. 2019;37(1):177-192. PubMed, CrossRef
- Pachori P, Gothalwal R, Gandhi P. Emergence of antibiotic resistance Pseudomonas aeruginosa in intensive care unit; a critical review. Genes Dis. 2019 Apr 17;6(2):109-119. PubMed, PubMedCentral, CrossRef
- Nasser M, Ogali M, Kharat AS. Prevalence of MDR Pseudomonas aeruginosa of war-related wound and burn ward infections from some conflict areas of Western Yemen. Wound Medic. 2018;20:58-61. CrossRef
- Danchy’n AO, Polishhuk MYe, Kazmirchuk AP, Danchy’n GO. Gunshot wounds of soft tissues of the skull’s vault. K.: Lazury’t-Poligraf, 2017. 116 p. (In Ukrainian).
- Gellatly SL, Hancock RE. Pseudomonas aeruginosa: new insights into pathogenesis and host defenses. Pathog Dis. 2013 Apr;67(3):159-73. PubMed, CrossRef
- Lutsenko TN, Kovalenko MV, Galkin OY. Validation of biological activity testing procedure of recombinant human interleukin-7. Ukr Biochem J. 2017 Jan-Feb;89(1):82-9. PubMed, CrossRef
- Kozhemyakin YuM, Hromov OS, Filonenko MA, Sajfetdinova GA. Scientific and practical recommendations for the maintenance of laboratory animals and work with them. Kiev: Avicenna, 2002. 156 p. (In Ukrainian).
- Romanenko ІІ. Prevention of internal-treatment infections in surgical profiles departments. Medsestrynstvo. 2017;(4):68-70. (In Ukrainian).
- Pokynbroda TYa, Каrpenko ІV, Midyana HH, Каrpenko ОYa. Isolation of surfactants synthesized by the Pseudomonas bacteria and study of their properties. Innov Biosyst Bioeng. 2019;3(2):70-76. CrossRef
- Namen AE, Schmierer AE, March CJ, Overell RW, Park LS, Urdal DL, Mochizuki DY. B cell precursor growth-promoting activity. Purification and characterization of a growth factor active on lymphocyte precursors. J Exp Med. 1988 Mar 1;167(3):988-1002. PubMed, PubMedCentral, CrossRef
- Goodwin RG, Lupton S, Schmierer A, Hjerrild KJ, Jerzy R, Clevenger W, Gillis S, Cosman D, Namen AE. Human interleukin 7: molecular cloning and growth factor activity on human and murine B-lineage cells. Proc Natl Acad Sci USA. 1989 Jan;86(1):302-6. PubMed, PubMedCentral, CrossRef
- Lee G, Namen AE, Gillis S, Kincade PW. Recombinant interleukin-7 supports the growth of normal B lymphocyte precursors. Curr Top Microbiol Immunol. 1988;141:16-8. PubMed, CrossRef
- Takeda S, Gillis S, Palacios R. In vitro effects of recombinant interleukin 7 on growth and differentiation of bone marrow pro-B- and pro-T-lymphocyte clones and fetal thymocyte clones. Proc Natl Acad Sci USA. 1989 Mar;86(5):1634-8. PubMed, PubMedCentral, CrossRef
- Andreu-Ballester JC, Cuellar C, Garcia-Ballesteros C, Pérez-Griera J, Amigó V, Peiró-Gómez A, Peñarroja-Otero C, Ballester F, Mayans J, Tormo-Calandín C. Deficit of interleukin 7 in septic patients. Int Immunopharmacol. 2014 Nov;23(1):73-6. PubMed, CrossRef
This work is licensed under a Creative Commons Attribution 4.0 International License.