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Recurrent infection with human alphaherpesvirus 1 (HHV-1) may be associated with immune exhaustion that impairs virus elimination. Thymic peptides enhance immune function and thus could overcome immune exhaustion. In this study, we investigated whether reactivation of herpes infections was associated with immune exhaustion. Moreover, we examined the impact of treatment with thymostimulin on the expression of programmed cell death protein 1 (PD-1) and its ligand (PD-L1) on T and B lymphocytes in patients suffering from recurrent HHV-1 reactivation. We also assessed the effector function of peripheral blood mononuclear cells (PBMCs) after stimulation with thymic peptides. We enrolled 50 women with reactivated HHV-1 infections and healthy volunteers. We measured the expression of various activation and exhaustion markers on the surface of PBMCs using flow cytometry. In ex vivo experiments, we measured the secretion of inflammatory cytokines by PBMCs cultured with thymostimulin. Compared with controls, patients with reactivated HHV-1 infections had increased percentages of CD3+ co-expressing CD25, an activation marker ( p < 0.001). Moreover, these patients had increased percentages of CD4+ and CD8+ cells co-expressing the inhibitory markers PD-1 and PD-L1. In cultures of PBMCs from the patients, thymostimulin increased the secretion of interferon gamma ( p < 0.001) and interleukin (IL)-2 ( p = 0.023), but not IL-4 or IL-10.Two-month thymostimulin therapy resulted in no reactivation of HHV-1 infection during this period and the reduction of PD-1 and PD-L1 expression on the surface of T and B lymphocytes ( p < 0.001). In conclusion, reactivation of herpes infection is associated with immune exhaustion, which could be reversed by treatment with thymic peptides.

Background: Purified thymus extracts (pTE) and synthetic thymic peptides (sTP) are thought to enhance the immune system of cancer patients in order to fight the growth of tumour cells and to resist infections due to immunosuppression induced by the disease and antineoplastic therapy., Objectives: To evaluate the effectiveness of pTE and sTP for the management of cancer., Search Strategy: We searched CENTRAL (The Cochrane Library 2010, Issue 3), MEDLINE, EMBASE, AMED, BIOETHICSLINE, BIOSIS, CATLINE, CISCOM, HEALTHSTAR, HTA, SOMED and LILACS (to February 2010)., Selection Criteria: Randomised trials of pTE or sTP in addition to chemotherapy or radiotherapy, or both, compared to the same regimen with placebo or no additional treatment in adult cancer patients., Data Collection and Analysis: Two authors independently extracted data from published trials. We derived odds ratios (OR) from overall survival (OS) and disease-free survival (DFS) rates, tumour response (TR) rates, and rates of adverse effects (AE) related to antineoplastic treatments. We used a random-effects model for meta-analysis., Main Results: We identified 26 trials (2736 patients). Twenty trials investigated pTE (thymostimulin or thymosin fraction 5) and six trials investigated sTP (thymopentin or thymosin α(1)). Twenty-one trials reported results for OS, six for DFS, 14 for TR, nine for AE and 10  for safety of pTE and sTP. Addition of pTE conferred no benefit on OS (RR 1.00, 95% CI 0.79 to 1.25); DFS (RR 0.97, 95% CI 0.82 to 1.16); or TR (RR 1.07, 95% CI 0.92 to 1.25). Heterogeneity was moderate to high for all these outcomes. For thymosin α(1) the pooled RR for OS was 1.21 (95% CI 0.94 to 1.56, P = 0.14), with low heterogeneity; and 3.37 (95% CI 0.66 to 17.30, P = 0.15) for DFS, with moderate heterogeneity. The pTE reduced the risk of severe infectious complications (RR 0.54, 95% CI 0.38 to 0.78, P = 0.0008; I² = 0%). The RR for severe neutropenia in patients treated with thymostimulin was 0.55 (95% CI 0.25 to 1.23,  P = 0.15). Tolerability of pTE and sTP was good. Most of the trials had at least a moderate risk of bias., Authors' Conclusions: Overall, we found neither evidence that the addition of pTE to antineoplastic treatment reduced the risk of death or disease progression nor that it improved the rate of tumour responses to antineoplastic treatment. For thymosin α(1), there was a trend for a reduced risk of dying and of improved DFS. There was preliminary evidence that pTE lowered the risk of severe infectious complications in patients undergoing chemotherapy or radiotherapy.

The results of treatment of 161 patients with diffuse forms of peritonitis with, using of the immunostimulators are analyzed. The algorithm of staged complex immunocorrection for patients with acute pancreatitis, including aged patients, is worked out. The use of it improves the results of treatment and allows decrease the morbidity.

The target of the case study was to investigate the efficiency of an alternative combined therapy scheme of herpes simplex infections versus the routine therapy by acyclovir or famvir as applicable to HIV-infected patients. leukinferon was shown to induce the antoherpetic acyclovir efficiency. The use of the latter concurrently with cycloferon for the treatment of infections provoked by herpes simple virus-1 (HSV-1) and HSV-2 in HIV-infected patients prolongs the remission period in case of the above opportunistic infections. The leukinferon anti-herpetic efficiency is, obviously, related with the phagocytosis stimulation and with its positive influence exerted on hemopoiesis. The combined therapy can be stated to be most effective in HIV, clinical stages B1 and 2.

Unlabelled: Compartmentalisation of mucosal immune response seems to be the result mainly of the preferential migration of activated cells back to their inductive sites. The aim of this report was to demonstrate, in a model of secondary immunodeficiency in Wistar rats (severely protein deprived at weaning and refed with casein 20%; group R21), that the oral administration of Thymomodulin (group:R21TmB) has different effects on gut and BALT (Bronchus-associated lymphoid tissue). Tissue sections (5 mu) were studied by immunohistochemistry 1). The oral administration of Thymomodulin restores only in gut Lamina propria (LP) the IgA B and CD4 T cell populations to control levels. The CD8a and CD25 subpopulations do not vary in gut as they return to control levels when refed with 20% casein diet. All the populations mentioned above remained decreased even after receiving Thymomodulin by the oral route. However, the same behaviour was observed for the TCR delta T cells that were decreased and return to normal levels in both mucosae by the effect of the immunomodulator; 2) when studying the iIEL (intestinal intraepithelial lymphocytes) CD8 alpha, CD25 and TCR gamma delta T cells, that were increased in R21, return to control levels in R21TmB. In BALT intraepithelium CD8 alpha and CD25 T cells remained decreased, while only TCR gamma delta T cells (increased in R21) return to control values., Conclusions: 1) there exists a compartmentalisation between both mucosae, as T CD4+ and IgA B+ cells are restored by TmB only in gut; 2) only those iIEL involved in inflammation (CD8 alpha+/CD25+ and TCR gamma delta+/CD25+) are normalised by means of the Thymomodulin 3) however, in BALT,only TCR gamma delta+ T cells are restored 4) the oral administration of the present immunomodulator may be useful as a therapeutic agent, although the preferential survival in the tissue of initial stimulation is the major factor in the preferential distribution of activated cells.

The paper presents the outcomes of surgical treatment in 117 patients with complicated liver echinococciasis in the past 9 years. Hepatic function and immunity, their pre- and postoperative changes in the combined use of essentiale and T-activin were studied. It has been found that the functional status of the liver, its detoxifying function in particular, largely impairs and immunosuppression develops in patients with complicated liver echinococciasis. The postoperative combined use of essentiale and T-activin led to the normalization of hepatic function and immunity. The combined treatment reduced the incidence of postoperative complications from 34.83 to 17.2%, such as acute hepatic failure, suppuration of a wound and a residual cavity, isolated abdominal abscesses, pleurisy, and pneumonia.

Due to disorders of hormonal balance in the organism, a decrease in thymic endocrine function occurred in rats after thyroidectomy. After removing the thyroid gland, we observed 1,3-2,2-fold decrease in the level of thymic hormone thymulin in the blood serum. When thyroxin was applied at a suppressive dose, endocrine function of the thymus did not restore. Injections of thymostimulin (Tp1) or its combination with thyroxin to thyroidectomized animals restored the level of thymulin up to the level in the intact rats due to effects of either injected preparation or induction of substances possessing thymosine-like activity.

Progressive ascitic growth of a spontaneous transplantable T-cell lymphoma, designated as Dalton's lymphoma (DL), in a murine host has been shown to be associated with an involution of thymus accompanied by a massive depletion of the cortical region and an alteration in the distribution of thymocytes by a decrease of CD4+CD8+, CD4+CD8- and CD4-CD8+ phenotypes caused by an enhanced induction of apoptosis in thymocytes. Moreover, an inhibition of humoral and cell mediated immune responses involving non-specific as well as antigen-specific T cell proliferative and cytolytic abilities with a decrease in the production of interferon gamma (IFNg) by the T cells of DL bearing mice has been observed. Results of the present study show that the administration of total thymic extract (TE) in DL bearing mice results in an increased survival of the DL bearing mice alongwith a significant increase in the weight of thymus and the total number of thymocytes with a lesser number of percent apoptotic thymocytes as compared to that in untreated DL-bearing mice. It is also shown that TE administration has a positive immunomodulatory effect on T cell functions as T cells obtained from TE administered DL bearing mice show an increased IFNg, production and an improved antigen specific proliferative ability. Moreover, the study indicates that TE acts directly on T cells as in an in vitro assay TE antagonised DL growth-associated induction of thymocyte apoptosis. Taken together, the results support the immunomodulatory function of the adult thymus and utilization of thymus derived factors as a potential immunotherapeutic agent for reversing tumor growth-associated immunosuppression.

Clinical and instrumental-laboratory investigations have been conducted in 372 patients with chronic antral gastritis (CAG, n = 131), diffuse gastritis (DG, n = 108) and ulcer disease (UD, n = 135). Immunomodulators tactivin and levamisol were added to standard treatment of 75 CAG, 63 DG and 85 UD patients. Healing of the lesions was observed, on the average, on the treatment day 24.3 +/- 0.5 and 18.4 +/- 0.6 in the standard treatment and with the added immunomodulator, respectively. Adjuvant levamisol diminished the number of recurrences of chronic gastritis and UD.

Immune status and condition of regional lymphoid tissue were studied in 28 patients with various forms of acute pancreatitis untreated with immunomodulating therapy and in 12 patients receiving combined therapy including lymphotropic regional therapy with T-activin. Acute pancreatitis patients were found to have aquired immunodeficiency, secondary autoimmune syndrome and reaction of toxic immune complexes the severity of which decreased under the action of T-activin therapy.

Regulating effect of thyroid hormones on functions of organs of the immune system has been demonstrated in the experiment. Deficiency of thyroid hormones affects thymulin synthesis and morphofunctional status of immunogenesis organs. Combination of thymostimulin and thyroxin in the thyroidectomized animals, as compared to their separate use, is pathogenetically the most adequate correcting therapy aiming normalization of structural and functional disorders in the thymus and spleen. Prolonged reaction of tissual basophils saturated with heparin, indicated hormonal activation of blood anticoagulative system, and complex of the above hormones can be used for prevention of thromboembolic complications.

Aim: To examine the functional status of the immune system in patients with lung and intrathoracic lymph nodes sarcoidosis and to evaluate the efficiency of immunomodulation alone and in its inclusion in combined treatment of the disease., Materials and Methods: 58 patients with the disease of varying severity were followed up. Comprehensive examination, involving clinical, immunological, X-ray, and physical studies, in patients treated with combined immunotherapy was performed. Initial examination revealed mixed immunodefficiency with impaired T- and phagocytic activity. According to the degree of immunological changes, the patients were given immunotherapy, including polyoxidonium, T-activin (or immunophan) injections, a complex of multivitamins and trace elements, and total adaptogens. After partial or complete normalization of an immunogram, all the patients received licopid (two-three 10-day courses, 10 mg/day)., Results: The optimal result (as long as 3-year remission) was achieved in the first time diagnosed sarcoidosis who have not taken glucocorticoidal hormones., Conclusion: The follow-up shows that addition of licopid is a compulsory component of immunotherapy in this disease; the efficiency of treatment is determined by its multimodality. The courses of therapy should be repeated when immunological indices deteriorated.

Immunofan and tactivin, employed as a means of immunological correction in the complex treatment of adenocarcinoma, decrease the onset frequency of radiation-induced complications and exhibit a pronounced immunocorrector effect. This was indicated by increasing level of lymphocytes (including CD3+, CD4+, CD8+, and CD19+), helper coefficient (CD4+/CD8+), and phagocyte activity of neutrophils, as well as by the tendency to normalization of the HCT-test results. Immunofan somewhat exceeds tactivin in the efficacy of endometrium adenocarcinoma treatment.

The immunomodulating and antimetastatic activity of clinically approved, low molecular weight, standardized thymic peptide (TP) preparations was evaluated in BALB/c-mice. Daily applications (subcutaneously, s.c.; intraperitoneally, i.p.; intramusculary, i.m.) of two commercially available TP preparations (7 consecutive days, 10, 50 and 100 micrograms per mouse and injection) up-regulated the thymus weight and thymocyte counts as well as peripheral blood leukocyte and lymphocyte counts in liver metastases-bearing mice. The immunomodulating activity of TP application was most pronounced and statistically significant for thymus weight and counts of thymocytes, leukocytes and lymphocytes after s.c. administration of both TP preparations and concentrations. I.p. and i.m. TP-injections were less effective at reaching statistical significance, however, for defined dosages and parameters, only. To evaluate the influence of TP on experimental liver metastases, RAW 117 lymphosarcoma cells were intravenously inoculated into BALB/c-mice. TP (10, 50, 100 micrograms/mouse) were s.c., i.p. and i.m. administered daily for 7 consecutive days starting 24 hours after tumor cell challenge. Liver colonization was investigated on day 14 after tumor cell inoculation and demonstrated a statistically significant (p < 0.05) reduction of experimental liver metastases for s.c. (both preparations and concentrations) as well as i.p. and i.m. (dose-dependent) TP-treated mice.

Persistent lymphopenia of various intensity has been noted in 45% of persons who had a history of infectIous mononucleosis. The group consisted od 500 patients, (236 males and 264 females). In all of them the diagnosis of mononucleosis had been based on the characteristic clinical signs and symptoms and changes in the blood picture and confirmed by the non-specific and/or specific serologic tests. In 33 persons (10 males and 18 females) the total number of lymphocytes varied from 884 to 992 per 1 cmm, the distribution being as follows: B lymphocytes--146 to 198, CD4--482 to 645 and CD8--245 to 364 per 1 cmm. 18 persons (18 males and 10 females) were given thymosine (TFX) subcutaneously for 30 days in the dose of 0.02 g daily, the remaining 15 (7 males and 8 females) received 3.0 g of isoprinosine per day for the same period. The total lymphocytes count and that of B, CD4 and CD8 was performed before and after the treatment and then followed once a month until 180 days since the treatment had been started. The TFX therapy was repeated after 8-12 months since the end of the first course in 3 patients and that with isoprinosine in 4. The strategy and the examination pattern were the same as before, control examinations being performed every 6 months and final analysis was done after 5 years of follow-up. Among the 33 patients who received immunomodulating treatment, normalisation of the lymphocytes count appeared in 24 (64%). Among the 12 persons with less pronounced lymphopenia, who did not received any treatment, spontaneous normalisation appeared in 5 (40%). It may be therefore assumed, that in persons with the history of infectious mononucleosis with persistent marked lymphopenia, thymosine and isoprinosine may be used in the therapy as additional immunomodulators.

A total of 44 patients with lung carcinoma underwent combined treatment involving systemic enzyme therapy with Wobe-Mugos E. In conducting radio- and polychemotherapy, the above enzyme therapy did not complicate the postoperative course, with the pyo-septic complications having gotten reduced, the origination of pneumofibroses prevented.

The systemic enzymotherapy using Wobe-Mugos E in the combined treatment of 32 patients with pulmonary cancer and of 21 patients with malignant thymoma was applied. After the chemotherapy and radiotherapy conduction the reduction of the postoperative septic-purulent complications, the pneumofibrosis occurrence prophylaxis was noted.

We report our initial clinical experience with local transrectal application of enzymatic treatment for chronic nonbacterial prostatitis and prostatodynia in 20 patients. Using a specially designed symptom score for evaluation of subjective treatment parameters, a statistically significant improvement of symptoms was found in the areas of pain, micturition, and recreational activities. No statistically significant differences were noted in laboratory values before and after treatment. Minimal local side effects were seen in only one patient. A favorable clinical response was noted in 75% of patients, whereas the remaining 25% showed only moderate improvement of symptoms. No patient experienced complete treatment failure.

Experimental series of 60 cotton rats and 150 white mice infected with echinococcus showed that 80-100% glycerin and 3% peroxide solution were effective scolicidal solutions for inactivation of the parasite. 344 patients have been operated on for hydatid disease with inactivation of the parasite by means of these scolicidal solutions. Glycerin during the surgical management of the hydatid cysts is effective and harmless in uncomplicated hydatid liver disease and any hydatid pulmonary cysts. Glycerin is contraindicated in complicated hydatid liver disease because of immunity disturbance. In complicated hydatid liver disease management of the hydatid cysts by 3% peroxide is effective and harmless. It is necessary to correct the hydatid liver disease patients' immunity in the preoperative and postoperative periods. Tactivin and antiechinococcus drug SK-1 are effective immunomodulators in hydatid liver disease.

Streptosotocin was administered to 21 test animals and 19 control ones. Preventively, the former were given T-activin, the latter--saline. 73% of the test animals were free of hyperglycemia, insulinopenia, activation of lipid peroxidation, morphologic evidence of beta-cell damage. In control animals diabetes mellitus arose in 84% manifesting with marked hyperglycemia, insulinopenia, LPO activation, morphological signs of beta-cell damage, lymphocytic infiltration of the islets. From the results obtained it can be concluded that T-activin has a prominent protective effect against diabetes mellitus (chi-square = 6.34, p < 0.05) which can be explained by its antioxidant and immunotropic activity.

Edema-swelling of the brain (ESB) is among the urgent problems of modern medicine. The purpose of the research was the study of the effect of immunotropic agents on formation of the pathologic process. It was demonstrated on a model of toxic ESB that taktivin and levamisole possess antiedemic activity. The effect is dose-dependent and is determined by the structural characteristics of the drugs under study. Unlike taktivin, large doses of levamisole demonstrate synergism with the effect of the edematous factor.

Oral enzymes act as a potent antiinflammatory, antiedematous agents thereby decreasing acute toxigenic effect of radiation and increasing compliance, quality of life of our patients. Fifty patients were randomized 25 allocated in enzyme and radiotherapy arm, 25 in radiotherapy alone. Pre RT and post RT biopsies were taken from both arms. In our study it was found that there was clinical, histopathological as well as statistical significant difference in both arms. The enzyme arm patients had mucostis of grade I in 76%, grade II in 12%, grade III in 8% while as 8% had grade I, 68% grade II, 24% had grade III in RT arm alone. In enzyme patients skin reactions of grade I in 72%, 20% had grade II, 8% had grade III. In control arm 12% had grade I, 76% had grade II, 8% had grade III skin reaction.

Background: Several studies showed that PGE-mediated immunosuppression in cancer patients may be differentially affected by conventional oncologic therapy., Methods: Since there is little evidence about the action of immunotherapy on this suppression mechanism, we investigated the effect of therapy with a thymic agent-T-activin, on in vitro modulation of lymphoproliferative response (LPR) by indomethacin., Results: The results demonstrated that indomethacin added in vitro enhanced LPR in early stage melanoma patients before therapy. T-activin therapy as an adjunct to surgery improved this lymphocyte function; the post-therapy in vitro addition of indomethacin did not significantly affect mitogen response. However, in those patients whose LPR was insufficiently enhanced by immunotherapy (3/8), indomethacin had improved their lymphocyte response. In the control patient group treated by surgery alone, indomethacin significantly enhanced LPR in vitro six months after operation. Although obtained in a small number of patients, our results indicate that the enhancing effect of T-activin therapy on lymphoproliferative response may be, at least in part, due to the effect on PGE-mediated suppressor cell activity., Conclusions: Furthermore, post-therapy in vitro testing may indicate a possible usefulness of this drug combination in some of the early stage melanoma patients.

Systemic enzymes (wobenzime and wobe-mugos) were approved, that had been prescribed as part of polychemotherapy to 24 patients with malignant lymphomas, who presented with large masses of lymphatic nodes poorly resorbable against the background of polychemotherapy and who were assigned for a high-total dose irradiation, which fact would undoubtedly entail sclerosing of adjacent intact tissues. The use of the enzymes made for the optimum realization of the polychemotherapy effect and permitted avoiding a good many of undesirable side events and complication thereof. The above systemic enzymes are well tolerated by patients; they induce no significant changes in the cellular composition or in blood biochemical indices.

Fifty six patients with pulmonary tuberculosis were examined. Of them 30 had T-activin in multimodality treatment. To supplement the agent in elderly and old patients was found to elevate the counts of T lymphocytes and T helper cells, to normalize Tx/Tc ratios, to enhance T lymphocytic activity and IL-2 synthesis. At the same time there was an increase in nonspecific responsiveness: enhancement of NKC activity and IL-1 synthesis by macrophages. With this, stimulation of specific antituberculous immunity took place. Normalization of immunological responsiveness and stimulation of specific antituberculous immunity were associated with enhanced therapeutical efficiency.

Previous studies on the effect of the oral administration of bacterial immunomodulators (1M-104 and RN-301) during the protein free diet period, have shown an increase on B and T cell gut repopulation, accompanied by IgA antibody production. The usefulness of oral administration of the immunomodulator thymomodulin (TmB) during the protein refeeding period was investigated. TmB allowed the recovery of a normal repopulation of gut lamina propria with IgA B and CD5 T cells and decreases to control values the number of activated intraepithelial lymphocytes (CD25+ T cell subset). Therefore, the oral administration of TmB may be useful as a therapeutic agent as it seems to improve the repopulation of intestinal villi with immunocompetent cells. Also, it seems to regulate the immunosurveillance at the epithelium level as it increases the CD5+ T cells but decreases the activated ones.

A complicated cataract on the only eye was effectively extracted in a patient with uveitis running a sluggish course with manifest disorders of T-cell immunity. Immune correction in combination with routine therapy of uveitis helped prepare the patient to surgery for cataract and attain good results.

2 groups of patients operated on knee joints for traumatic injuries were examined. In the study group endolymphatic drug therapy was carried out in postoperative period, in control group of patients conventional way of intramuscular administration of preparations was used. During the treatment, plasmatic cells, macrophages and tissue basophiles in synovial liquor were studied as well as synthesis of nucleic acids (DNA and RNA) in plasmatic cells. It was shown that immune homeostasis of synovial liquor in postoperative period normalized faster in endolymphatic administration. The studies of tissue basophiles have shown that inflammatory process in the knee joint is completed faster when endolymphatic route of drug administration was used. Clinical results evidence of higher effectiveness of endolymphatic therapy in comparison with conventional method of treatment in postoperative period. In the former case the inflammatory process was completed by the 5th day, in the latter--by the 7th-9th day. The endolymphatic therapy in all the patients resulted in healing of operation wounds by primary intention. In the group of patients treated by standard methods, suppuration of the wound was detected in 6 from 27 patients and postoperative synovitis in 7-9 days was observed in 6 patients.

We studied the effects of regional lymphotropic immunostimulating therapy on alterations in immunoglobulins levels both in blood serum and paranasal sinuses mucosal secretion in patients with acute and chronic purulent sinusitis. Solutions of tactivin, lidase and novocain were administered into the area of the submaxillary lymph nodes. The effect was compared to that obtained after subcutaneous administration of tactivin and conventional therapy. No reliable alterations in systemic humoral immunity in response to lymphotropic immunostimulating therapy was reported in acute sinusitis, while in chronic sinusitis an increase in initially low IgA occurred. Regional lymphotropic administration of tactivin promoted a pronounced decrease in the initially elevated levels of SIgA, IgA and IgG in the secretion of paranasal mucosa in acute purulent sinusitis, and an increase of basaline lowered SIgA, a fall in the IgG concentration in chronic purulent sinusitis. This is indicative of effectiveness of this method of immunostimulator administration on local immunological reactivity of the mucous membrane.

Eleven lung cancer patients were selected for combined radio and immunotherapy with a thymic agent-Thymex L. The selection criteria included the pre-therapy testing of patients' immunocompetence and the responsiveness of their lymphocytes to the in vitro addition of Thymex L: only patients with a significant degree of immunodepression, whose depressed cellular immunity parameters (the number of total and active T cells and their mitogen-induced lymphoproliferative response) were significantly increased upon this agent's action in vitro, entered the study. The results of the pre-therapy in vitro stimulation correlated with those obtained after completion of radioimmunotherapy: the administration of Thymex L along with radiotherapy seances prevented iatrogenic deterioration of initial depression of general immunocompetence and enabled to overcome it to a certain degree. This indicates that pre-therapy in vitro testing has a true predictive value. However, the initial immune disturbances were not normalized by immunotherapy; the post-therapy testing of the patients' lymphocytes to the addition of Thymex L in vitro showed that these cells possessed a residual potential to respond by a significant increase of the active T cell number and proliferative capacity, suggesting that immunotherapy could be prolonged in order to potentiate cellular immunity in immunodepressed lung cancer patients.

To evaluate the effect of thymostimulin in a treatment schedule of concurrent hyperfractionated chemoradiation therapy, with the cytostatic forming part of each therapeutic fraction, the authors included in this protocol 36 patients with advanced head and neck carcinomas randomized into two groups. Group A received 115 cGy + 5 mg/m2 of carboplatin per fraction in two daily fractions for a total dose of 8.050 cGy + 700 mg of carboplatin, while group B received the same treatment associated with thymostimulin, with the following schedule: 1.5 mg/kg/day in the week before chemoradiation + 1.5 mg/kg twice a week during treatment + 1 mg/kg twice a week for two years or until recurrence. The results were evaluated upon reaching 18 months of follow-up (30 maximum). A smaller decrease in lymphocyte levels was observed in group B, but no differences were seen in toxicity between the groups. Patients included in the B group had a slightly longer disease-free-survival interval, but 17% of recurrences and 11% of distant metastases were observed in the A group, whereas 22% of recurrences and 22% of distant metastases were seen in the B group. The number of complete remissions (94%) was the same in both groups.

Effects were traced out of vilosene alone and combination with ketotifene on clinical-and-immunologic parameters in 86 children with rheumatism associated with concurrent allergy. There has been disclosed immunomodulating effect of vilosene in hyposuppressor variant of a secondary immune deficient state in rheumatic children. Antiallergic action of vilosene is more pronounced when employed in combination with ketotifene. The clinical effect was evident 1-1.5 weeks earlier than in controls. The data obtained suggest vilosene and ketotifen to be useful in the treatment of rheumatic children presenting with concurrent allergy.

A sharp decrease in the characteristics of nonspecific protection and humoral immunity in mixed infections (Pseudomonas aeruginosa + fungi of the genus Candida) in cases of burn traumas was established. Under these conditions an increase (up to 100%) in the number clones with the signs of pathogenicity and multiple medicinal resistance in the populations of infective agents, accompanied by a high death rate among the animals (up to 60%), was observed in the dynamics of the infectious process. The use of immunomodulators (tactivin and sodium nucleinate + lidocaine) contributed to the restoration of the phagocytic function of peripheral blood lymphocytes and humoral immunity, as well as to a decrease in the death rate of the animals. At the same time a considerable decrease in the number of clones with the signs of pathogenicity was observed in the populations in infective agents, isolated from the animals in the process of treatment.

We conducted a prospective randomized study to assess the effect of thymostimulin in patients with long-standing chronic obstructive pulmonary disease (COPD) during a 1-year follow-up. A total of 38 patients in the intervention group and 40 in the control group received standard treatment for COPD. Patients in the intervention group were also given thymostimulin intramuscularly (1 mg/kg day for the 1st week followed by once a week for 6 months). At the end of the study period, patients treated with thymostimulin showed a statistically significant lower number of exacerbations and hospital admissions as compared with controls. However, there were no changes in the number of patients with severe or moderate impairment of respiratory function throughout the study period. No significant differences were found by Multitest or in serum concentrations of immunoglobulins and T-cell subsets before and after thymostimulin treatment. We conclude that treatment with thymostimulin is effective in the prevention of COPD exacerbations acting on the cellular immune response involved in bronchopulmonary defense.

Patients with head and neck carcinoma show deficits of cellular immunity, probably due to low molecular mass factors (LMMFs) released by the tumour. Thymostimulin (TP1) restores the defective monocyte chemotaxis and dendritic cell clustering capability in the presence of the tumour when administered pre-operatively. In the present study we investigated these immune parameters in 39 patients treated with TP1 for 10 days pre- and 6 months post-operatively and in 22 patients who were not treated with TP1 for 6 months after operation. Removal of the tumour in non-TP1-treated patients also resulted in a restoration of monocyte and dendritic cell functions, while TP1 treatment gave no additional effect. LMMF levels in the blood of both TP1-treated and non-TP1-treated patients remained elevated even after removal of the tumour, and it is therefore concluded that it is unlikely that depression of cellular immunity is a direct effect of these LMMFS.

Original immunological studies allowed the authors to design a combined treatment of laryngeal papillomatosis (LP) with administration of immunomodulators and cytostatics. Surgery was performed on demand. Thymic hormone preparation (T-activin, thymalin, thymogen) and prospidin served as immunomodulators and cytostatic, respectively. To create lymphotropism, prospidin was delivered by means of electrophoresis following subcutaneous introduction of 8--16 U lidase. Sensitivity of patients to thymalin was tested in vitro by thymalin-induced changes in the number of CD2--DR+ lymphocytes. Adjuvant modalities were age-adjusted dibasol as inductor of interferon genesis and adaptogens (eleutherococcal fluid extract, B and C vitamins). Such treatment was given to 39 children. Remission duration increased 1.6--2.6-fold, 6 of 7 children with primary LP achieved persistent remission. Positive changes in immunological indices occurred in 84% of children. The above treatment outcomes support the efficacy of the method in childhood LP.

Background: Head and neck squamous cell carcinoma (HNSCC) produces immunosuppressive low-molecular-mass factors (LMMFs) responsible for defects in the cell-mediated immune system. These defects include impaired monocyte chemotaxis and an impaired capability of dendritic cells (DC) to form cellular clusters. It has been shown previously that the immunomodulating drug thymostimulin (TP1) restores these defects in vitro., Methods: An immunohistochemical study was performed on tumors of 18 patients with HNSCC who had preoperatively been treated with TP1 in one of three dosages (0.5 mg/kg, 1.0 mg/kg, 2.0 mg/kg body weight). Additionally, tumors of 4 patients who had been treated with a placebo and 12 patients who had not received any preoperative treatment were studied. A relative surface area of infiltration, meaning the percentage of stromal or epithelial tissue covered by infiltrating cells in histological sections, was calculated using an image analysis system (VIDAS RT) for CD3+ T-cells, CD14+/CD68+ monocytes/macrophages and L25+/CD1a+ dendritic cells for each tumor., Results: A highly significant, denser T-cell infiltration into the stromal tissue area of tumors of patients who had been treated with TP1 when compared with tumors of non-TP1-treated patients was observed for all three dosages. None of the other tumor-infiltrating cell types was affected by TP1. In addition, a correlation was found between the tumor T-cell infiltration and capability of DCs in the peripheral blood to form clusters with T-cells. No correlation existed between CD3+ T-cell numbers in peripheral blood and T-cell infiltration into the tumor; nor were monocyte chemotactic functions in peripheral blood correlated with tumor infiltration by monocytes or monocyte-derived macrophages and DCs., Conclusions: Preoperative treatment of HNSCC patients with TP1 appears to strongly enhance tumor--T-cell infiltration. The number of tumor-infiltrating DCs was not affected by TP1, but a positive correlation between tumor--T-cell infiltration and DC clustering capability suggests that the functional status of DCs is important in improved cell-mediated immunity.

Clinicoimmunological characteristics were followed up in the course of laryngeal papillomatosis (LP) in 96 children. It was found that they had suppressed T-cell immunity, phagocytosis which still worsen with the disease aggravation and recurrences. A decrease in nonspecific resistance, properdin, lysozyme, complement and secretory IgA indicated impairment of nasopharyngeal and laryngeal local immunity. A scheme of combined treatment is proposed incorporating basic therapy with reaferon, systemic immunomodulators (thymalin, T-activin) and local immunocorrection. Such approach reduced the time of basic treatment and prolonged remission 2.5-3-fold.

The use is studied of the immunomodulating agents splenin and vilosen in a combined therapy of 93 patients with chronic cholestatic disorders of the liver. The above drug combination was found to have a positive effect on both the immune status and condition of microhemodynamics, with the clinical parameters getting improved, duration of remission lengthened.

The influence of immunoactive medicines on the cell immunity have been studied. There were differences in reaction to T-activin and Thymalin between various patients with septic postoperative complications. Thymalin stimulated T-cells while acting with immunoglobulins or immune plasmas only. T-activin led to the increase in the number of T-lymphocytes and B-lymphocytes independently of it's cooperation with the vaccines. The stimulating effect of myelopid demonstrated itself by increase in the number of B-lymphocytes and immunoglobulins M and G after 14 days of treatment. The positive clinical effect was more impressive when immunomodulators were used in combinations with the vaccines; still it did not correlate completely with the dynamics of the cell immunity parameters.

Monotherapy with methotrexate (MT) was compared to combined therapy MT+tactivin (T) in a 2-year clinical trial including 127 patients with rheumatoid arthritis (RA). MT was given to 88 patients in a weekly dose 7.5 mg. In 39 patients this dose was given in combination with subcutaneous injections of T (100 micrograms two times a week for a months, then once a week). Both treatments induced a significant decline in severity of arthralgia, in the number of joints with inflammation, in the level of C-reactive protein and in ESR. Morning stiffness and pains in the joints at palpation were achieved after MT+T combination. Side effects were similar in both treatments.

We investigated the clinical and immunological effects of T-activin therapy in early stage melanoma patients. Several immune parameters (the number of T cells-E-RFC and CD3+, their subsets-CD4+ and CD8+, the number of CD38+ and CD16+ cells, and mitogen-induced lymphoproliferative response-LPR) were analyzed in relation to the clinical course of the disease in patients treated by T-activin in addition to the surgery (n = 8), and in control patients treated by the surgery alone (n = 9). Immunological tests were performed before therapy and one month after the last (6th) cycle of T-activin, i.e. six months after surgery in controls. The patients were followed-up from February 1991 to August 1995. Clinical evaluation showed that disease-free interval for observed period was similar in both groups of patients (17.5 and 13 months), while the survival time was longer in T-activin-treated patients than in controls (40 vs. 24 months), although this difference was not significant. The phenotyping analysis of peripheral blood lymphocytes showed no changes of the pretreatment values of total T cells and their subpopulations regardless the clinical course of the disease in both groups of patients. The number of NK cells (CD16+) was significantly increased after T-activin therapy, but this increase was not associated with clinical benefit, since it was seen in patients with the progression of the disease. In control patients, the initial number of CD16+ cells did not change significantly, irrespective of the clinical course. The lymphoproliferative response increased significantly in 4 out of 5 T-activin-treated patients with the progression of the disease, while a slight increase of this lymphocyte function was seen in 3 disease-free patients. In patients treated by surgery alone, especially those with disease progression, the LPR was significantly decreased six months after tumor excision. These findings, although obtained in small number of patients, suggest an immunomodulatory action of T-activin therapy in early stage melanoma patients, which did not correlate with the clinical course of the disease. On the other hand, an almost doubled survival time in T-activin-treated patients in comparison to the controls, may indicate a possible effect of T-activin therapy on some other immune functions not evaluated in this study. Further investigations in a larger number of patients is needed for assessment of the true effectiveness of such therapy.

Sixty-three patients with congenital and acquired defects and deformations of facial bones without concomitant diseases were examined. Twenty-eight of them were operated on; auto- and alloplasty was resorted to in 18 patients, and to 10 patients tactivin was administered after common protocols for immunocorrection before or after surgery. Immunologic and clinical studies showed that immunodeficiency states are the most probable causes of postoperative complications following repair surgery on the facial bones. Tactivin normalized the immunity parameters and prevented the development of postoperative complications.

Examinations of 46 patients with acute inflammatory diseases of the maxillofacial area revealed a reduction of some immunity parameters. Thymic activity of the saliva and blood was found to reduce still more after surgery (opening of the phlegmon). The ratio of thymic activities of the saliva and blood may be an indirect evidence of a tendency in development of an inflammatory process. The authors demonstrated the efficacy of correcting immunity parameters by tactivin, which was particularly effective in grave cases. Tactivin concentrations in the blood and saliva, their time course and ratio may be considered as additional criteria for assessing the status of patients and the risk of complications.

Results were studied of use of T-activin in those clinical settings related to acute inflammatory diseases of the kidneys. There was a positive clinical effect from this preparation in all twenty-eight patients with acute purulent pyelonephritis, accompanied by readjustments in the patients' immune system. A rise to the norm was found to occur in T-helper counts, and accordingly, immunoregulatory index, NK-cell activity, blood microbocydic activity. The in vitro investigations done suggested the need for individual testing of immunocompetent cells of the patient to optimize the therapy.