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Purpose: Local ionizing radiation (IR) can lead to systemic lymphocyte depletion, which is associated with poor survival outcomes in patients with cancer. Interleukin-7 (IL-7) plays an important role in lymphocyte homeostasis; however, its role in alleviating radiation-induced lymphopenia remains unclear. Hence, we established a radiation-induced lymphopenia animal model and evaluated the effect of exogenous IL-7 administration., Methods: C3H/HeN mice underwent x-ray irradiation of 30 Gy in 10 fractions at the right hind limbs. Next, 10 mg/kg of IL-7 was injected subcutaneously, and the lymphocyte count in blood was measured. Murine hepatocellular carcinoma (HCa-1) cells were inoculated subcutaneously into the right thighs of tumor model mice, which underwent the same treatment., Results: In the naïve mouse model, the decreased CD45 + cell count after irradiation gradually recovered to the initial level over 3 weeks in the IR group, whereas it markedly increased to 373% of the initial level in 1 week in the IR+IL-7 group. Similar trends were observed for the CD3 + , CD8 + , CD4 + , regulatory T cells, and CD19 + B cell counts. Similar findings were observed in the tumor mouse model. CD8 + and CD4 + T cell infiltration in tumor specimens was higher in the IL-7 and IR+IL-7 groups than in the nontreated and IR groups. Tumor growth was significantly more suppressed in the IR+IL-7 group than in the IR group. The median survival time was significantly longer in the IR+IL-7 group (not reached) than in the IR (56 days; P = .0382), IL-7 (36 days; P = .0004), or nontreated groups (36 days; P < .0001)., Conclusions: Administration of exogenous IL-7 after IR not only restored lymphocyte counts but also enhanced the antitumor effect. Exogenous IL-7 can be beneficial in overcoming radiation-induced lymphopenia and in enhancing the treatment outcome in combination with radiation therapy, which needs validation through future clinical studies., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Objectives: Lymphocyte depleting therapies have been used to treat refractory autoimmune disease, including RA, but treatment may be associated with long-term lymphopenia. It is unclear whether delayed reconstitution preferentially affects lymphocyte subsets, how this modulates immune challenges and whether thymic function influences the outcome. These questions are now addressed in a detailed analysis of RA patients 12 years after alemtuzumab (anti-CD52) treatment., Methods: Blood was obtained from 20 RA patients 12 years after alemtuzumab treatment. Lymphocyte subsets were enumerated by flow cytometry. T-cell receptor excision circles (TRECs)/ml were determined to quantify thymic function, and serological responses to neoantigens and recall antigens were assessed., Results: RA patients remained lymphopenic 12 years after their first dose of alemtuzumab. CD5(+) B cells, which may be associated with autoantibody production, were significantly reduced in alemtuzumab-treated patients compared with age-matched disease controls. In addition, naïve and memory CD4(+) T-cell subsets were present in altered proportions in patients who had received alemtuzumab, with increased effector memory CD4(+) T cells, and decreased naïve and central memory CD4(+) T cells. TRECs were detectable in alemtuzumab-treated patients and correlated with CD4(+) lymphocyte counts. Vaccine responses to neoantigens and recall antigens fell within the normal range for an ageing population., Conclusions: Alemtuzumab therapy resulted in long-term alterations in lymphocyte subsets. The significance of these changes remains uncertain but patients respond normally to antigenic challenges. Thymic function remains an important determinant of T-cell reconstitution even several years after lymphocytotoxic therapy.

Unlabelled: We report on two brothers with hyperimmunoglobulinemia D (patient 1: serum immunoglobulin D [IgD] concentration initially 61 IU/ml, later on 340 IU/ml; patient 2: serum IgD concentration 144 IU/ml; normal <100 IU/ml, 97th centile) and periodic fever syndrome (HIDS). Both are compound heterozygous for the mevalonate kinase (MVK) mutations V377I and I268T. They developed significant B cell cytopenia (7%, 129/microl and 11%, 132/microl, respectively; normal ranges 12-22%, 300-500/microl) with hypogammaglobulinemia (IgG 5.48 g/l and IgG 5.22 g/l, respectively; normal range IgG 6-13 g/l). Furthermore, the clinical spectrum shows an interesting atypical autoinflammatory symptomatology. The therapy consisted of prednisone, azathioprine, and intravenous immunoglobulins (IVIG), which results in reduced incidence and severity of febrile attacks., Conclusion: The pathogenesis and clinical presentation of HIDS is still not fully understood and show a great variability. To our knowledge, severe B cell cytopenia in children with HIDS has not been reported before. Furthermore, the therapy of febrile episodes is still performed on an individual basis in affected patients.

A selective B-lymphocyte-differentiating tripeptide, bursin, H-Lys-His-Gly-NH2, and its 10 analogs were synthesized by a solid-phase method and were tested for their effect on reduced B lymphocytes of uremic patients. Incubation of peripheral lymphocytes isolated from uremic patients with the synthetic bursin showed an enhancing effect on the reduced B lymphocytes. Of the s synthetic analogs, [Sar3]bursin exhibited the most potent effect.

A positive immunomodulatory effect was found in chronic bronchitis patients examined immunologically before and after treatment including chlotazol. T- and B-cell immunity recovered, clinical condition of the patients improved. A combination of known antimicrobial and antiinflammatory effects with an uncovered immunomodulatory one made chlotazol a valuable modality in the treatment of chronic bronchitis associated with secondary immune deficiency.

Results of the investigation of 89 patients with the amebic abscess of the liver are presented which are divided into 4 groups depending on the clinical form of the disease and the immunological state. A correlating relationship was established between the functional state of the liver and changes of the immunological status of the organism. Variants of complex therapy of patients with the amebic abscess of the liver are proposed.

The study of the time course of immunocytologic structures of a lymphocyte pool in newborns with sepsis has shown a direct dependence of these parameters on the period of the disease. The lymphocyte sensitivity to thymomimetcs in the tests in vitro, as well as the level of the immunoregulatory index reflect most completely the clinical effect of these preparations, that serves an objective criterion for the use of immunocorrecting drugs in the therapy of a generalized bacterial process.

Forty patients with Hodgkin's disease were examined for cell-mediated immunity. Analysis of peripheral blood showed a decrease in the relative and absolute E-RFU counts depending on the disease stages. The changes in B-cells bearing surface immunoglobulins were negligible. E-RFC (T-cells) prevailed in the spleen of patients with Hodgkin's disease. However, some of the patients had a high enough count of B-cells in the spleen and peripheral blood. Multiple modality treatment for Hodgkin's disease, radiation therapy in particular, aggravated disorders of cell-mediated immunity. Thirty-one patients received levamisole at the definite stages of multiple modality treatment with a purpose of correcting cell-mediated immunity disorders. Two schemes of levamisole intake were tried. The drug was given in a dose of 150 mg for 21 days, the total dose amounting to 3, 150 mg, or in a dose of 150 mg for 4 days with a 10-day interval, the total dose being 2, 100 mg. Only two patients noted side effects one of them had a "gas taste" in the mouth, whereas the other one skin itch and urticaria that did not require any treatment. Application of levamisole increased the relative and absolute E-RFU counts, absolute lymphocyte count. Patients on levamisole noted the improvement of the well-being.

The time course of quantitative and functional parameters of humoral and cellular immunity, autosensitization to pancreatic tissue was studied in 200 patients with chronic pancreatitis. It was shown that different clinical types of the disease were characterized by different types of immune shifts. Correlation was found between clinical and immunological indices. Immunosuppressive influence of protease inhibitors in chronic pancreatitis was shown. Incorporation of the immunomodulator levamisole in therapeutic measures made it possible to prolong remission and to reduce recurrence frequency.