Defects in functioning of interferon and immune systems and their correction in chronic active Epstein Barr infection

摘要

Creating of new methods of treatment of patients with chronic active Epstein-Barr virus (EBV) infection is a very actual problem. The activation of EBV infection may occur in connection with major disturbances of interferon (IFN) system and immune system (IS). The aim of our study was to research the IFN system, main antiviral mechanisms of IS in patients with atypical chronic active EBV infection and to create new methods of IFN- and immunotherapy for treatment of this disease. We had studied 35 patients (both sexes in age of 20 - 50 years), suffering from atypical chronic active EBV infection associated with chronic fatigue syndrome, prolong mild pyrexia, nonexudative pharyngitis, tonsillitis, lymphadenopathia. EBV infection was tested by PCR and serological methods and was found in 100% of cases. Levels of induced production of IFNa and IFNgamma were tested for the assessment of the IFN system. Numbers of CD3~+, CD3~+CD4~+, CD3~+CD8~+, CD3~+CD56~+, CD4~+CD25~+ CD4~+HLA-DR~+, CD8~+HLA-DR~+, CD8~+CD25~+, CD3CD16~+CD56~+, CD3CD16CD56~+, CD56~+HLADR~+, CD19~+ cells , levels of serum IgG, IgM, IgA, numbers of neutrophilic granulocytes(NG) and activity of theirs reactive oxidative species (ROS) production by chemoluminescense method were researched before and after treatment. Defects of IFN system were found in 100.0% of cases: impairments of induced production of IFNa had place in 100.0%, induced production of IFNgamma - in 82.8% of cases. Different defects of T chain (deficiencies of CD3~+ and/or CD3~+CD4~+, and/or CD3~+CD8~+, and/or CD3~+CD56~+, increasing level of CD4~+CD25~+ lymphocytes) were tested in 80.0% of patients. Low levels of NKs (CD3~- CD16~+CD56~+ and/or CD3~- CD16CD56~+) were tested in 77.1% of cases. Deficiencies of serum IgG and/or IgM took place in 42,8% of patients. Dysfunctions of NG (neutropenia, defects of ROS production) were revealed in 74,3% of cases. In the issue all patients had had different combine disturbances of IFN and immune systems. We had created program of combine IFN- and immunotherapy including: a) the base prolonged continuous systemic IFN therapy by recombinant N PHIHalpha2 Viferon, using differential doses (at the first step in dose 6 Mln.IU during 4 weeks and then the gradual dose reduction every 4 weeks), course of Viferon treatment was longed 4.5 months; b)restoration of T chain of IS with using of 10 days courses of Isoprinosine monthly during 4.5 months; c) for reconstruction of NK, NG, humoral chain Licopid was used (2mg/daily during 10 days, then supporting dose - 2mg/daily 3 time a week - 1 month, then 2mg/daily 2 time a week - 1 month). We had used the alternation of courses of Isoprinosine and Licopid. At the first step of treatment synthetic drug Famvir was used for better elimination of EBV: 1000mg daily during 14 days. If it was necessary course of Famvir was repeated in acute period. As result of treatment the regression of chronic fatigue syndrome, prolong mild pyrexia, nonexudative pharyngitis, lymphadenopathia had observed after 2-3 weeks from the beginning of IFN and immunotherapy. We could see the preservation of the positive clinical effects after 1 year from the end of the treatment. Positive dynamic of changes in IFN and immune systems were observed in 77.7% of patients. Thereby IFN- and immunotherapy allow to achieve positive clinical and immunological efficiencies in atypical chronic active Epstein-Barr virus infection.