Immunomodulation in vitro. The predictive value of in vitro testing of lung cancer patients' lymphocyte responsiveness to stimulation by Thymex L. A preliminary report.

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.

[In vitro reactivity of lymphocytes after the addition of immunostimulatory drugs]. / Reaktivnosti limfocita in vitro na dodavanje imunostimulacionih sredstava.

The in vitro immunomodulating, effects of two thymic extracts--Thymex L and Thymomodulin--on lymphocytes of lung cancer patients, were studied. The number of total and active T cell and PHA-induced lymphoproliferative response were evaluated before and after the addition of two different concentrations (5 mg/ml and 0.5 mg/ml) of these agents. The in vitro incubation with Thymex L and Thymomodulin had no effect on the number of total T lymphocytes, but the active T cells and proliferative responses were significantly higher. This increases was observed in the majority of patients with diminished baseline values. These results indicated that several immunological parameters should be used in vitro testing of an immunomodulatory drug. They also indicated the need for in vitro testing selection of candidates for immunotherapy among immunodepressed cancer patients.

[Immunomodulating effect of thymus protein fraction on disorders of general immunity in patients with lung carcinoma]. / Imunomodulatorna dejstva proteinske frakcije timusa na poremecaj opste imunosti u bolesnika sa karcinomom pluca.

The parameters of both cellular and humoral non-specific immunity were evaluated in non-small lung cancer patients (n = 26) prior to therapy, in 13 of them after radiotherapy (45 Gy in 22 fractions) and in 13 patients after combined radio-and immunotherapy (Thymex L, 1800 mg in 12 injections á 150 mg i.m., three times a week). Several parameters of general immunocompetence were altered in patients even before any therapy. The radiotherapy caused more severe immunologic disturbances, the cellular immunity being affected more profoundly. Thymex L., when given simultaneously with radiotherapy, prevented this deterioration in a majority of patients.

Enhancement of phytohemagglutinin-induced lymphoproliferative response by indomethacin, Thymex L or their combination in lung cancer patients.

Several studies showed that thymic factors and prostaglandin synthesis inhibitors enhance in vitro lymphoproliferative response (LPR) to mitogens in cancer patients. In this study we investigated whether indomethacin and thymic extract (Thymex L), applied in combination, may in a synergistic pattern influence phytohemagglutinin-induced LPR in lung cancer patients. The results demonstrate that the use of the investigated agents enhances LPR to a similar level in hyporeactive patients before, as well as after, therapy. However, this drug combination exerts an additive effect on LPR, but only in patients who underwent cytoreductive radiation therapy, indicating the potential usefulness of this drug combination as an adjuvant treatment of these patients.

The protective activity of Thymex L against radiotherapeutically-induced cellular immunodepression in lung cancer patients.

In order to prevent the radiotherapeutically-induced aggravation of initial immunodeficiency, a thymic preparation (Thymex L) was given to lung cancer patients simultaneously with irradiation. The parameters of both cellular and humoral nonspecific immunity were evaluated in two groups of patients: one was treated with radiotherapy only (60 Gy in 30 fractions); the other one received Thymex L (100 mg 3 times a week, total dose 1800 mg, i.m.) simultaneously with radiotherapy. The significant decrease of B and T cell number, and decreased lymphoproliferative response to PHA were found in all patients before therapy; the number and phagocyting capacity of blood monocytes, as well as the concentrations of circulating IgG, IgA and immunocomplexes, were all significantly increased. Immediately after irradiation the patients had even lower number of T and B cells, diminished reactivity to PHA and higher number of mononuclear phagocytes when compared to the values before therapy. In patients treated with Thymex L, the number of B and T cells and PHA-induced proliferative response were significantly higher than in those treated with radiotherapy only. No effect of this therapy was seen on active T cells, on high number and function of mononuclear phagocytes and on elevated concentrations of serum immunoglobulins and immune complexes. Our results indicate that Thymex L can successfully prevent the harmful effect of radiation therapy on cellular immunity in a majority of lung cancer patients.

[Immunologic disorders in lung malignancies and possibilities of immuno-corrective therapy]. / Imunoloski poremecaji kod malignoma pluca i mogucnosti imunokorektivne terapije.

The nonspecific immune competence was investigated in three groups of patients with bronchogenic lung cancer: group I (n = 30) was tested prior to any therapy; group II (n = 8) after radiotherapy; and group III (n = 13) after the end of combined radio and immunotherapeutical (Thymex-L) treatment. A total of 46 healthy persons served as control group. Both cellular (the number and function of T cells and mononuclear phagocytes) and humoral (the number of B cells and the levels of serum immunoglobulins and immune complexes) immune reactivity were tested. The number of T cells and B cells, as well as their function, were markedly depressed in a majority of patients before therapy; the number and reactivity of phagocytes were significantly higher in patients than in controls. The radiologic treatment caused further decrease of T cell number and function. The number of phagocytes was significantly higher than before radiotherapy. This treatment had no effect on the parameters of humoral immunity. All these parameters were less affected in patients who were simultaneously treated by irradiation and Thymex-L; no effect was seen on the humoral immunity, except the immune complexes, which returned to normal values only in that group of patients.

[Sarcoidosis with an unusual clinical course]. / Sarkoidoza neuobicajenog klinickog toka.

Sarcoidosis is a disease which in 90-100% affects the thorax and other organs in 20-50%. Although a systemic disease, its pathohistologic verification concurrently performed in different organs is most interesting. A case of a patient with sarcoidosis and pathohistologic examination of bioptic material revealing sarcoid granuloma in mediastinal glands, liver and parotid gland is reported together with clinically evident eye and central nervous system involvement.

[Dressler's syndrome during radiotherapy in bronchial carcinoma]. / Dresslerov sindrom u toku zracne terapije karcinoma bronha.

A case of Dressler's syndrome which has developed in a patient with bronchogenic carcinoma during radiotherapy is presented. Diagnosis is established according to symptomatology, clinical findings, chest X-ray, laboratory analysis and immunological findings. Existence of metastatic deposits in heart is excluded by the method of echocardiography. Short-term cardiologic therapy with antiflogistics is completely sufficient for maintaining the stability of "cardiologic status".