ISSN 2415-3060 (print), ISSN 2522-4972 (online)
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УЖМБС 2017, 2(3): 43–47
Clinical Medicine

Nonspecific Immune Response Peculiarities to Influenza Vaccination in Patients with Diabetes Mellitus

Grishyna O. I.1, Babinets O. M.1, Menkus O. V.1, Myroshnychenko T. M.2

The purpose of the study is to examine the indices of cellular immunity, interleukin-4 (IL-4), interferon-γ (IFN-γ) before and 3 weeks after vaccination against influenza in patients with type 2 diabetes. 67 patients with type 2 diabetes who made up the group "1" were examined. The control group "2" included 30 healthy persons. Among the patients with diabetes there were 31 (46%) women and 36 (54%) men aged 43 to 79 years, whose mean age was (M ± SD) (63.1 ± 15.8) years. In the control group, there were 14 (47%) women and 16 (53%) men aged 42 to 77 years, whose mean age was (M ± SD) (60.7 ± 17.8) years. Thus, the groups were comparable by sex and age. The diagnosis of diabetes was established based on the diagnostic criteria of the International Diabetes Federation (International Diabetes Federation, 2011). Insulin resistance was determined using the HOMA (The Homeostasis Model Assessment) index. Determination of the number of lymphocytes in peripheral blood with CD antigenic determinants was performed using monoclonal antibodies "Anti-CD4", "Anti-CD8" (Granum, Ukraine). The level of insulin in the blood serum was determined by the enzyme immunoassay using sets of ready-made reagents produced by DRG, Germany. IL-4 and IFN-γ were determined in the blood serum by a solid-phase enzyme immunoassay using sets of ready-made reagents "Interleukin-4-IFA-BEST", "Interferon-γ-IFA-BEST", (Vector-Best CJSC, Russia) respectively. The statistical analysis was carried out using the Microsoft Office 2007 Excel statistical software package. The threshold for the statistical error of different tests was set at 5%. The nature of the descriptive statistics depended on the type of variables. To compare the data, the t-test (Student), Wilcoxon and the chi square test were used. The NOMA-index before vaccination in groups "1" and "2" was (4.5 ± 1.8) vs (2.3 ± 0.6), p = 0.00. Also significantly higher NOMA-index was in group "1" 3 weeks after vaccination (5.2 ± 1.7) against (2.0 ± 0.6), p = 0.00. Unlike the indices of group "2", p = 0.06, in group "1" there was a significant increase in this index, p = 0.01. The level of CD4 + at the initial stage was significantly lower in the group "1" (24.4 ± 6.9)% vs (29.1 ± 7.4)% in the group "2", p = 0.03. After 3 weeks, this index in group "1" did not change, and in group "2" there was a significant increase in it: (26.5 ± 8.6)%, p = 0.12, against (33.5 ± 8.6)%, p = 0.04, in the group "2". Relative differences were also obtained between the groups after 3 weeks. A similar picture was observed when determining the CD8 + level: the primary indices in the group "1" were lower than those in the group "2": (19.6 ± 6.8)% against (23.0 ± 6.1)%, p = 0.02. After 3 weeks, the level of this indicator significantly increased in the group "2" (28.3 ± 8.7), p = 0.01. In the group "1", the CD8 + level was (21.8 ± 6.9)%, p = 0.07 compared to the baseline data and p = 0.00 compared with the group "2" data. The level of IL-4 in patients with diabetes did not significantly differ from that in healthy subjects before vaccination and increased 2.5 times after vaccination. At the same time, the content of IL-4 in SD patients after vaccination became significantly lower than in healthy individuals. This may serve as evidence of a smaller increase in Th2 cell activity. At the same time, the level of INF-γ, which was significantly lower before vaccination in diabetic patients compared with healthy individuals, increased more significantly after vaccination (by 2.9 times). Accordingly, the ratio of INF-γ / IL-4 after vaccination significantly increased, both within the group and in comparison with healthy individuals. As a result, we can assume the initial decrease in immunological activity in patients with diabetes and the imbalance of the immune system, which is manifested by greater activation of Th1 cells. At a high concentration of glucose in the blood, the systemic inflammatory response is strengthened due to excessive formation of free radicals, increased expression of cytokines and other mediators of inflammation, lymphopenia with a decrease in the number of CD4 + and CD8 + T cells. In addition, the regulatory function of CD4 + is impaired, which is manifested by different degrees of activation of Th1 and Th2 cells. Analyzing the obtained data, it can be concluded that the nonspecific immune response to influenza vaccination in patients with diabetes is characterized by a less pronounced increase in CD4 + and CD8 + T cells and an imbalance that manifests itself by a greater activation of Th1 cells compared to healthy individuals.

Keywords: vaccination, influenza, diabetes, immunity

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  1. Kukushkin GV, Starostina EG. Infektsii u bolnykh sakharnym diabetom (lektsiya). RMZh. 2016; 20: 1327–33.
  2. American Diabetes Association. Diagnosis and Classification of Diabetes Mellitus. Diabetes Care. 2011; 1: S62–S69.
  3. Fedson DS, Wajda A, Nicol JP, Hammond GW, Kaiser DL, Roos LL. Clinical effectiveness of influenza vaccination in Manitoba. JAMA. 1993 Oct 27; 270 (16): 1956–61.
  4. Fleming DM, van der Velden J, Paget WJ. The evolution of influenza surveillance in Europe and prospects for the next 10 years. Vaccine. 2003 May 1; 21 (16): 1749–53.
  5. Foster DA, Talsma A, Furumoto-Dawson A, Ohmit SE, Margulies JR, Arden NH, Monto AS. Influenza vaccine effectiveness in preventing hospitalization for pneumonia in the elderly. Am J Epidemiol. 1992; 136: 296–307.
  6. Hak E, Buskens E, Essen GA, de Bakker DH, Grobbee DE, Tacken MA, van Hout BA, Verheij TJ. Clinical effectiveness of influenza vaccination in persons younger than 65 years with high-risk medical conditions: the PRISMA study. Arch Intern Med. 2005; 165: 274–80.
  7. Mangtani P, Cumberland P, Hodgson CR, Roberts JA, Cutts FT, Hall AJ. A cohort study of the effectiveness of influenza vaccine in older people, performed using the United Kingdom general practice research database. J Infect Dis. 2004; 190: 1–10.
  8. Mullooly JP, Bennett MD, Hornbrook MC, Barker WH, Williams WW, Patriarca PA, Rhodes PH. Influenza vaccination programs for elderly persons: cost-effectiveness in a health maintenance organization. Ann Intern Med. 1994; 121: 947–52.
  9. Nichol KL, Baken L, Nelson A. Relation between influenza vaccination and outpatient visits, hospitalization, and mortality in elderly persons with chronic lung disease. Ann Intern Med. 1999; 130: 397–403.
  10. Nichol KL, Margolis KL, Wuorenma J, Von Sternberg T. The efficacy and cost effectiveness of vaccination against influenza among elderly persons living in the community. N Engl J Med. 1994; 331: 778–84.
  11. Nichol KL, Nordin J, Mullooly J, Lask R, Fillbrandt K, Iwane M. Influenza vaccination and reduction in hospitalizations for cardiac disease and stroke among the elderly. N Engl J Med. 2003; 348: 1322–32.
  12. Nichol KL, Nordin JD, Nelson DB, Mullooly JP, Hak E. Effectiveness of influenza vaccine in the community-dwelling elderly. N Engl J Med. 2007; 357: 1373–81.
  13. Nichol KL, Wuorenma J, Sternberg T. Benefits of influenza vaccination for low-, intermediate-, and high-risk senior citizens. Arch Intern Med. 1998; 158: 1769–76.
  14. Nordin J, Mullooly J, Poblete S, Strikas R, Petrucci R, Wei F, Rush B, Safirstein B, Wheeler D, Nichol KL. Influenza vaccine effectiveness in preventing hospitalizations and deaths in persons 65 years or older in Minnesota, New York, and Oregon: data from 3 health plans. J Infect Dis. 2001; 184: 665–70.
  15. Ohmit SE, Monto AS. Influenza vaccine effectiveness in preventing hospitalization among the elderly during influenza type A and type B seasons. Int J Epidemiol. 1995; 24: 1240–8.
  16. Puig-Barberà J, Diez-Domingo J, Pérez Hoyos S, Vareaag ÁB, Vidald DG. Effectiveness of the MF59-adjuvanted influenza vaccine in preventing emergency admissions for pneumonia in the elderly over 64 years of age. Vaccine. 2004; 23: 283–9.
  17. Puig-Barberà J, Márquez-Calderón S, Masoliver-Fores A, Lloria-Paes F, Ortega-Dicha A, Gil-Martín M, Calero-Martínez MJ. Reduction in hospital admissions for pneumonia in non-institutionalised elderly people as a result of influenza vaccination: a case-control study in Spain. J Epidemiol Community Health. 1997; 51: 526–30.
  18. Rao Kondapally Seshasai S, Kaptoge S., Thompson A, Di Angelantonio E, Gao P, Sarwar N, Whincup PH, Mukamal KJ, et al. Diabetes mellitus, fasting glucose, and risk of cause-specific death. The emerging risk factors collaboration. New Engl J Medicine. 2011; 364 (9): 829–41.
  19. Vaccines against influenza WHO position paper – November 2012. Wkly Epidemiol Rec. 2012; 87: 461–76.
  20. Voordouw BC, van der Linden PD, Simonian S, van der Lei J, Sturkenboom MC, Stricker BH. Influenza vaccination in community-dwelling elderly: impact on mortality and influenza-associated morbidity. Arch Intern Med. 2003 May 12; 163 (9): 1089–94.
  21. Wallace T. M. Use and Abuse of HOMA modeling [Text] / Wallace TM, Levy JC, Matthews DR. Diabetes Care. 2004; 27: 1487–95.
  22. Wang ST, Lee LT, Chen LS, Chen TH. Economic evaluation of vaccination against influenza in the elderly: an experience from a population-based influenza vaccination program in Taiwan. Vaccine. 2005; 23: 1973–80.