[The lymphocyte transformation test using mononuclear cells of elderly humans as a suitable in vitro method for testing of structure activity relationships of splenin peptides]. / Der Lymphozytentransformationstest unter Verwendung von mononukleären Zellen alter Menschen als geeignete in vitro-Methode zur Testung von Struktur-Wirkungs-Beziehungen von Splenin-Peptiden.

More and more new immunostimulatory substances are developed. Besides old and new drugs have to be examined with regard to their side effects. Hence it follows demands for effective test possibilities. The lymphocyte transformation test with mononuclear cells of old men is a suitable in vitro method for testing of substances with thymic hormone-like activity in order to investigate the structure-effect-relationships. Thymopentin, human splenopentin and human diacetyl-splenopentin increase the phytohaemagglutinin induced lymphocyte transformation, on the other hand in the case of bovine splenopentin and human splenotritin this effect was not observed. By means of a patient with hypogammaglobulinaemia is demonstrated that the lymphocyte transformation test could also be a suitable method for the estimation of pharmacodynamics such peptides after in vivo treatment.

Mitigating effects of dialysable leukocyte extract (DLE) on the experimental allergic uveitis (EAU) of the rabbit.

Experimental allergic uveitis (EAU) is an induced autoimmune disease by administering soluble retinal S antigen and complete Freund's adjuvant (CFA). In rabbits, the result is the occurrence of chorioretinitis in 90% of the cases. The first inflammation is followed by spontaneous relapses. The EAU of the rabbit was utilized to study the effects of the dialyzable leucocyte extract (DLE) on the course and the intensity of the disease in this autoimmune model. The DLE preparations examined differed with regard to their origin or the immunological stimulation of the initial material (DLE from humans (DLE Hu) and DLE from the normal rabbit (DLE RaO) or rabbits which had EAU (DLE RaEAU) and rabbits which had received CFA (DLE Ra (CFA). One unit of DLE corresponds to the extract from 10(9) cells. The administration of DLE starts with the onset of inflammation. 4 x 0.5 units were administered during the first week, 1 x 0.5 units per week from the 2nd to the 12th week. All preparations decrease the cumulative frequency of the days of illness significantly. The duration of the initial inflammation is reduced in all animals treated, but only in part significantly. There appears a graduation of efficacy: DLE RaEAU greater than DLE Ra CFA greater than DLE Hu greater than DLE RaO. Overall, it can be seen that, on the one hand, there is no specificity or restriction of the species for the efficacy and, on the other hand, the extent of the effects depends on the degree of the immunological stimulation. The maximum efficacy of DLE RaEAU is not exclusively due to the transmission of an antigen-specific sensitization.(ABSTRACT TRUNCATED AT 250 WORDS)

Clinical, biochemical and immunological effectiveness of diacetyl-splenopentin (BCH 069) in hay fever.

Diacetyl-splenopentin (BCH 069) is a new pentapeptide of splenin modified by twofold acetylation. BCH 069 has thymopentin-like activity demonstrated by in vivo animal and in vitro human studies. Two groups of patients received 50 mg BCH 069 and placebo, respectively, by subcutaneous injection 3 times weekly for 4 weeks. The third group of patients received 50 mg BCH 069 by intravenous injection 3 times weekly for 6 weeks. The therapy was carried out during the peak of the pollen season. BCH 069 intravenous treatment was found to be significantly superior to placebo treatment in reducing clinical symptoms. Biochemical inflammatory signs were not observed. No increase of bronchomotoric reactivity was established in comparison to the placebo group. There was a significantly lower increase in gras-spollen specific IgE and IgG4 in the intravenous group of BCH 069. Subcutaneous therapy with BCH 069 was not effective. The study demonstrated that BCH 069 used intravenously induces clinical improvement in patients suffering from hay fever. Thus the possibility to influence hyperreactive conditions of the immune system has been confirmed. The study indicates that various application routes of BCH 069 have different effects on the immune system.

Platelet membrane defects in fawn hooded bleeder rats.

An inbred strain of fawn hooded rats with a congenital platelet defect shows a marked bleeding tendency with prolonged bleeding time. This haemorrhagic disorder has been exclusively related to a deficiency of nucleotides in platelet dense granules. When tested in cell electrophoresis platelets from fawn hooded bleeder rats showed a significantly lower electrophoretic mobility than normal rat platelets. Subsequent studies on the platelet membrane protein pattern by high resolution two-dimensional gel electrophoresis revealed the deficiency of a membrane glycoprotein (apparent molecular mass 90.000, isoelectric point 5.6), which is detectable in normal rat platelets after surface labeling by periodate-tritiated sodium borohydride. It seems likely, that this glycoprotein defect contributes at least partially to the disorder of platelet function in fawn hooded bleeder rats.

[Immunological status of patients with recurrent herpes simplex infections. In vitro effect of thymopoietin and splenin-derived and partially modified peptides on peripheral blood lymphocytes in comparison to a thymus extract]. / Immunologische Befunde bei Patienten mit rezidivierenden Herpes-simplex-Infektionen. In-vitro-Einfluss von Thymopoietin und splenin abgeleiteten und teilweise partiell modifizierten Peptiden auf Blutlymphozyten im Vergleich zu einem Thymus-extrakt.

Immunological studies on 20 patients with frequently recurrent Herpes simplex labialis were performed. Disorders of the cell-mediated immunity were often observed which do not only occur during the relapses. The number of T cells and their function were especially reduced. On the other hand there were no alterations of the CD4/CD8 ratio and the suppressor-activity. In vitro studies with peptides of thymopoietin and splenin justify the assumption that these peptides have therapeutic effects in recurrent herpes simplex infections.

[Age-dependent sensitivity of human lymphocytes to the immunomodulating effect of bovine and human diacetyl splenopentin]. / Altersabhängige Sensitivität humaner Lymphozyten gegen die immunmodulatorische Wirkung von bovinem und humanem Diacetyl-Splenopentin.

Both newborns and elderly adults suffer from physiological immunodeficiency. The molecular mechanisms responsible for this immunodeficiency are currently investigated by many laboratories. The aim of our investigations was to answer the question wether these immunodeficiencies could be influenced by bovine and/or human diacetyl-splenopentin, two newly developed immunostimulatory peptides. The in vitro effects of these peptides were studied using the lymphocyte transformation test and the detection of the immunoglobulin production (IgG, IgM) by lymphocytes. Thymopentin was used as standard for these investigations. The age dependence of lymphocyte sensitivity was estimated using cells of the following groups of blood donors: newborns (cord blood); young donors (20-30 yr); old donors (over 70 yr). All peptides were shown to have the same effects. The stimulated lymphocyte proliferation (PHA, anti-CD3) was inhibited in young donors and further increased in old donors. There was no influence in the case of newborns. The biological activity of human diacetyl-splenopentin was shown to be higher in comparison with bovine diacetyl-splenopentin.

[The effect of long-term dialysable leukocyte extract therapy on the recurrence behavior of idiopathic uveitis]. / Wirkung einer DLE (Dialysable Leukocyte Extract)-Langzeittherapie auf das Rezidivverhalten der idiopathischen Uveitis.

26 patients with idiopathic uveitis (anterior uveitis 11, intermediate uveitis 8, posterior uveitis 7) were treated with Dialysable Leukocyte Extract (DLE) for a long period. In comparison with the period before DLE in anterior and posterior uveitis the numbers of relapses decrease, the inflammation-free intervals become longer. These prolongations are significant. In cases with intermediate uveitis such a significance is not available. But in all types of uveitis DLE therapy shortens the duration of inflammatory episodes. These effects lead to a highly significant decrease of the portion of the period during and after DLE therapy in which inflammatory signs occur in comparison with the period before DLE therapy. The latter result becomes evident for all types of uveitis.

Lymphocyte activation by low doses of cyclosporin A.

Supernatants of human lymphocyte cultures incubated with cyclosporin A (CS-A) for 90 min reveal an inhibitory effect on the electrophoretic mobility of guinea-pig macrophages. This effect is distinctly demonstrable already at CS-A concentrations from 10-7 micrograms/ml on with a maximum at 10-3 micrograms/ml. An inhibitory action of CS-A on PHA-induced lymphocyte proliferation is detectable only beyond 10-2 micrograms/ml CS-A. The CS-A induced lymphokine is comparable to that stimulated by other ways (PHA, ConA).