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The immunological reactivity was studied in 152 patients with pulmonary tuberculosis of whom 112 suffered also of alcoholism. All patients with association of the two diseases showed inhibition of the functional activity and reduction of the number of T-lymphocytes while those without alcoholism showed these changes in 80%. Use of T-activin and electrophoresis of chlorophyllypt allowed to restore the moderately reduced reactivity in most patients. In markedly reduced inhibition of cellular immunity T-activin proved more effective.

Thirty-four patients with AIDS-related complex (ARC) were treated for 6 months with thymostimulin, a thymic hormone. Clinical and immunological findings after a 1-year follow-up were compared with those in 24 age- and sex-matched controls receiving no immunotherapy. Statistical evaluation after 6 and 12 months showed significant differences in the two groups. The thymostimulin-treated group had higher leukocyte and lymphocyte counts, more positivity in intradermal tests with multiple recall antigens, and less lymphadenopathy and weight loss. The number of OKT3+ and OKT4+ lymphocytes decreased significantly in the control group, but did not change in the thymostimulin-treated patients. Finally, after 18 months of follow-up, no progression to AIDS was seen among the treated subjects, whereas 3 of the controls developed the disease. We conclude that thymostimulin, alone or in combination with antiviral drugs, may be helpful in the management of ARC patients.

Two children with chronic Epstein-Barr virus infection were treated with a standardized thymic hormone preparation (thymostimulin, TP-1 Serono). The treatment was well tolerated. No adverse reactions, no side effects were observed. Results of immunological investigations showed a trend towards normalisation. Additional clinical evidence showed up, which pointed to a response to the therapy.

The use of T-activin in combination with chemical drugs allowed to markedly increase efficacy of the treatment. As a result of the treatment significant improvement was found in 17 (41.5 per cent) out of 41 patients with marked disorders in cellular immunity and severe tuberculosis. At the same time in the patients treated with the chemotherapeutics alone the improvement was stated only in 18.5 per cent of the patients. T-Activin improved the indices of cellular immunity and eliminated imbalance in regulatory subpopulations of T-helper and T-suppressor cells.

Secondary immune deficiency generally involves more profound defects in cellular than humoral immunity. This type of immune deficiency occurs in acquired immunodeficiency syndrome (AIDS), cancer, malnutrition, aging and following immunosuppressive therapy. Immunorestorative therapies were developed for use in the immunotherapy of cancer. Their experimental use in cancer and other diseases such as infections and autoimmunity has demonstrated their safety and their capacity to improve host responses to disease particularly when the host is immunocompromised. Biologicals such as the thymic hormones and interferon have been intensively studied and are briefly reviewed in this paper. Chemically defined drugs such as levamisole, isoprinosine, azimexon, and muramyl dipeptides have also been extensively analyzed and the action of certain purine-related compounds are discussed to exemplify their immunopharmacologic features. The combined uses of biologicals and drugs are suggested to improve the efficiency of immunotherapy.

Numerous trials of prophylaxis of recurrent respiratory infections in children have been performed, even though the only controlled trials providing incontrovertible results were the ones carried out with levamisole and thymostimulin through intramuscular administration. We have experimented a calf-thymic extract administered by oral route (thymomodulin). During the summer we enrolled 40 children aged between 3.5, and 9 years who had suffered from RRI during the previous winter. The patients were randomly divided in two groups and respectively treated with thymomodulin or with placebo; 21 children were given the thymic extract and 19 the placebo. The trial was carried out according to a double-blind schedule for a period of four months, from the beginning of October '84. At the end of the trial we assessed the catharral bouts observed during the research period by the family doctors and the parents evaluation on the clinical state. The difference between the two groups is statistically highly significant both with reference to the reduction of the total number of catharral bouts and to the general clinical state according to the parents opinion. The research clearly demonstrates the protective effect of the thymomodulin, probably due to the "restorative" effect on some immunological functions, temporarily compromised during the infection bouts.

Twenty-eight infants with bronchiolitis were randomized divided into two groups. Clinical diagnosis was made by scores indicated by the Bronchopneumology Study Laziale. Group one received thymostimulin (TP-1 Serono: 1.5 mg/kg/die for five days), while in the second group it was not administered. Interferon concentration in frozen serum (-20 degrees C) was evaluated at entry and after 48 hours. Etiology, severity grade and clinical characteristic were similar in both groups; this has made reliable the present evaluation. Although, in the first four days clinical score was slightly lower in the first group than in the second, there were not observed differences with statistics significance and hospitalization was similar in both groups. Because there has been described in literature an increase in interferon's production after TP-1 administration we evaluated the influence of this hormone on interferon's production. There were no differences with statistics significance with or without treatment. This study has not showed an important TP-1's efficiency in the treatment of bronchiolitis.

An infant with partial trisomy 22 syndrome and recurrent infections showed severe cellular immunodeficiency and serum IgG reduction. A marked increase of E-RFCs was observed after in vitro incubation of peripheral blood lymphocytes with thymostimulin (TS), a calf thymic extract. The treatment with TS resulted in reduction of infections, correction of cellular immunodeficiency and increase of IgG levels. Such a primary thymic hormone dependent immunodeficiency may be due to an altered development of branchial arches, commonly present in trisomy 22 syndrome. The same pathogenetic mechanism may account for thymus dysplasia observed in other chromosomal syndromes.

A 25-day-old Chinese female baby developed necrotizing fasciitis (NF) with indurated erythematous patches with superficial necrosis over two thirds of the back. Skin cultures of the lesions yielded Streptococcus pyogenes, enterococcus, Pseudomonas aeruginosa, and Candida species. The patient had lymphopenia with low T cells and T cell subsets. The lymphoproliferative response to mitogen and macrophage migration (MIF) production were also poor. Her lymphocytes were unable to produce IgG in vitro. Also, IgG bearing cells were not demonstrable. The initial lymph node biopsy demonstrated an absence of follicular formation and depletion of lymphocytes in both thymic-dependent and thymic-independent areas. Five weeks after bovine thymic extract (Thymostimulin) treatment, a second lymph node biopsy demonstrated germinal centers containing IgG bearing cells. Three weeks later, a third lymph node biopsy showed germinal centers with cuffs of lymphocytes. Differentiation of the cortex and medulla of the node was demonstrated. IgG was also detectable in an in vitro Ig synthesis study. The total T cells, T cell subsets, lymphoproliferative response MIF production also increased gradually after Thymostimulin treatment. This investigation demonstrated the therapeutic effectiveness of Thymostimulin in NF with underlying combined immuno-deficiency, both serious and frequently fetal diseases, by the histologic and immunologic reconstitution of T and B cell function.

Studies in a variety of animal and human models indicate that thymosin plays a role in the differentiation of a number of T-cell subpopulations. The hypothesis presented is that a normal immune balance depends heavily upon the presence of thymosin-activated suppressor or regulator T-cells. A major thrust in our present research program is to determine whether or not the various disorders discussed here are causally related to abnormal thymosin production by the thymus gland. We are also assessing in animal models the potential value of thymsin in the treatment of specific autoimmune diseases. This information may yield new insights for the management of autoimmune type disorders such as SLE. Results from clinical trials to date suggest that thymosin will have a role in boosting the immune responses of patients with specific thymic malfunctions and may indeed exert an influence via the production of suppressor or regulator T-cells.

A generalized state of immunosuppression during surgery has been implicated in the development of septic complications postoperatively. We studied 18 patients operated upon for benign diseases, to examine the influence of surgical trauma on circulating lymphocyte subpopulations in man. Additionally, we evaluated the effect of thymostimulin on these changes, in another group of 10 patients. Our results suggest that the total number of lymphocytes, as well as lymphocyte subpopulations CD3+ and CD4+, fell significantly following surgery. This reduction in cell number is more pronounced on the helper/inducer lymphocytes. The CD4+/CD8+ ratio decreases significantly after operation. For patients with no complications, the immunosuppression in terms of peripheral lymphocyte population, seen in the postoperative period is usually reversible around the seventh day. On the other hand, peripheral blood lymphocyte changes in the postoperative period were less pronounced in patients treated with thymostimulin. Thymostimulin's action is predominantly on T lymphocytes, and within these, on the T helper/-inducer subpopulation. And finally, thymostimulin is capable of maintaining a normal relationship between helper/inducer and suppressor/cytotoxic cells (CD4+/CD8+ ratio) during the postoperative period, suggesting a better immune state.

Infectious and allergic bronchial asthma in patients living under unfavourable environmental conditions occurs at the background of decrease of theophylline-sensitive E-POL and metabolic acidosis. Stage-by-stage complex immune correction helps to counterbalance environmental impact on the immune system and to raise significantly treatment efficacy.

The rate of postoperative infections is significantly increased in anergic patients. The authors evaluated prospectively, in a controlled, randomized and stratified study, the efficiency of thymostimulin in reducing postoperative infections in 42 such patients. Excluded were those who were malnourished in whom preoperative alimentation corrected the anergy. The incidence of infections was significantly (p less than 0.05) reduced in thymostimulin-treated patients (4.8% versus 28.6%).

The efficacy of immunomodulating agent T-activin has been studied in adult BALB/C mice infected with Coxsackie B1 virus. Optical, electron microscopic and immunological tests have shown that T-activin protects myocardium and modulates immune disorders in mice with viral myocarditis.

In our investigations on rats was proofed the qualification of substances 2-Cyanoethyl Urea (CEH), Thymus-Extract and Lithium-carbonate for a potential reducing or shortening of the leucocyte-depression after whole-body irradiation. Intravenous applications of 2-Cyanoethyl Urea in Wistar rats showed no effect not only in the increase of leucocytes but also in variation in portions of leucocytes. In our investigations we could not influence radiogenic phase of leucopenia by application of CEH after 7 Gy whole-body irradiation. Intramuscular injections of thymus extract don't influence the number of leucocytes in peripheral blood in irradiated Wistar rats. The differential blood-count was uninfluenced. Increase in concentration of thymus extract and also higher frequency of the applications effect no changes in blood-count. Leucocyte depression after whole-body irradiation was independent of the application modus of thymus extract. Lithium-carbonate shows a significant increase of leucocytes in peripheral blood in dependence of dosage and frequency of application. After whole-body irradiation with 7 Gy under lithium therapy it was shown that on day 6th after irradiation leucocyte number was significantly higher than in controls. Radiogenic leucopenia phase was reduced significantly by lithium.