Influence of various forms of dialyzable leukocyte extracts on rat adjuvant arthritis.

Adjuvant-induced arthritis in rats is a chronic inflammatory disease, widely used as an animal model for rheumatoid arthritis. In our study the effect of various fractions of dialyzable leukocyte extract (DLE): DLE I-molecular weight below 10 kDa (commercial preparation), DLE II-molecular weight below 5 kDa (suppressor fraction), DLE III-molecular weight 5-10 kDa on rat adjuvant-induced arthritis was studied. The adjuvant arthritic (AA) rats were treated with DLE fractions i.p. in solutions containing an active substance isolated from 12.5 x 10(6) and 6.25 x 10(6) leukocytes from day 1 (adjuvant injected) through day 18, every second day (total 9 times). Various markers of inflammation, immune function and joint destruction were evaluated: hindpaw volume, serum hyaluronic acid, serum albumin and biopterin in urine. All these markers showed a significant improvement after using fraction DLE II in comparison with AA controls. Fractions DLE I and DLE III influenced only some markers of inflammation and immune function. Our results demonstrated a therapeutical effect of fraction DLE II on rat adjuvant-induced arthritis.

In vitro production of the factors effective in the transfer of experimental autoimmune aspermatogenesis.

We studied the biological effects of the factors released into the culture medium by the lymphocytes from animals sensitized with testicular antigen. The supernatants from cultures of these lymphocytes were active in vitro in the migration inhibition tests because they transferred the sensitivity to normal spleen cells. In vivo, they transferred aspermatogenesis in the allogeneic and xenogeneic system. The results suggest a specific effect on the behaviour of macrophages rather than a direct cytotoxic effect of the active factors.

Influence of thymosterin on immunological reactivity in New Zealand mice.

The influence of thymosterin on immunological reactivity of NZB mice was investigated. Thymosterin was administered three times per week for a period of six weeks to male and female NZB mice. Only lymphocytes from untreated female mice gave the positive results in the macrophage migration inhibition test using native DNA as the stimulating antigen. This effect was suppressed in thymosterin treated females. The administration of thymosterin therefore appears to correct the in vitro delayed hypersensitivity to DNA antigen.

Age-dependence of spontaneous delayed hypersensitivity to DNA, antinuclear antibody production and development of glomerulonephritis in NZB mice.

In NZB mice of different ages (2, 4, 8, 12, and 16 months) the positivity of the migration inhibition test performed with the ds-DNA in spleen explants was compared with the level of immunofluorescent antinuclear antibodies and the incidence of glomerulonephritis. The positivity of the MIT was apparent at 4 months of age, rose with ageing and decreased after 12 months of age. Production of ANA began later, mostly at 8 months of age, increased progressively with ageing, especially in female mice, and was followed by the development of glomerulonephritis which reached its peak at 16 months of age.

Clinical and immunological characterization of systemic lupus erythematosus in patients with circulating interferon and migration inhibitory factor.

The simultaneous occurrence of interferon and migration inhibitory factor was found in sera from 9 patients with systemic lupus erythematosus (SLE). Their clinical picture was characterized by a moderate course of the disease. In 7 patients the inflammatory tendoarticular manifestations were accentuated. Glomerulonephritis was found only in 3 patients and was successfully suppressed by immunosuppressive therapy. In the peripheral blood of most of these patients, normal or moderately increased levels of active E-rosettes were found. Therefore we consider these SLE patients as a group with characteristic signs of activated cell-mediated immunity (lymphokine release, active E-rosettes). Although the reason for this activation remains unknown, we suppose that some concomitant bacterial infection, perhaps mycobacterial, may contribute to this immunological phenomenon.

Influence of antilymphocyte and antipolymorphonuclear sera on the pyrogenic effect of scarlet fever toxin.

The role played by lymphocytes in the pyretic response to scarlet fever toxin (ET) was studied in vivo using antilymphocyte serum (ALS). Two i.v. injections of ALS inhibited the pyretic response to a subsequent ET injection in rabbits. The course of endotoxin fever remained uninfluenced by ALS. Antipolymorphonuclear serum had no effect on the pyretic response to either of the toxins. Pretreatment with ALS also inhibited the skin reaction after i.d. injection of ET. These findings are further evidence a mediating role of lymphocytes in the biological effects of ET, among other things in the release of endogenous pyrogen.

In vitro studies of cell-mediated immunity in rabbits sensitized with Mycobacterium kansasii and Mycobacterium tuberculosis.

Rabbits, sensitized with M. kansasii, responded by a profound inhibition of migration of macrophages elicited by both antigens: the migration index for homologous antigen was 0.51 in the direct test and 0.65 in the indirect test; for heterologous antigen the indexes were 0.53 and 0.67. However, significant differences in reactivity were found in rabbits sensitized with M. tuberculosis. In the homologous system, high reactivity was maintained and the migration index reached the value of 0.53 in the direct and 0.63 in the indirect test. On the other hand, the heterologous antigen M. kansasii influenced the migration in both direct and indirect assays significantly less, the migration indexes being 0.62 and 0.72. The differences were statistically significant at 1% and 5% levels.

Cell-mediated immunity to varicella-zoster virus as assessed by the migration inhibition test.

The migration inhibition method was used to test cell-mediated immunity to varicella-zoster (VZ) virus in 10 varicella and 11 herpes zoster patients. Control groups consisted of eight children susceptible to VZ infection on serological evidence and 49 normal persons of different age categories. Depending on the positivity criterion adopted, positive results during disease were obtained in 43% or 90% or all tests performed in varicella patients and 47% or 74% in herpes zoster patients. Irrespective of which criterion of positivity was applied, a high rate of positive results was obtained in the normal control groups; in the age range from 20--44 years it was comparable to that for patients. This finding would suggest a high activity of VZ virus among the human population. Since a positive result in migration inhibition test offers evidence of recent contact with antigen, either exogeneous contact with VZ infection or endogenous contact with latent VZ virus must have been involved.

The effect of native and sonicated double-stranded polyribonucleotides on the course of spontaneous autoimmune disease in NZB and NZB/Swiss F1 mice.

The administration of sonicated fractions of f2 phage polyribonucleotides caused an increased weight loss and deterioration of the clinical state in female NZB mice. Discontinuance of the treatment resulted in an improvement of both the clinical state and the genetically determined autoimmune disorders of these mice. Some potential explanations of this effect are discussed.

[Control of autoimmune processes by natural and other non-harmful methods]. / Kontrola autoagresivních procesu pomocí prirozených a dalsích pro organismus neskodných postupu.

At present an increase of some autoaggressive diseases can be observed. The commonly used treatment consists of the administration of some immunosuppressive drug of some hormonal preparations. This type of therapy is accompanied by some undesired side effects, as these drugs influence also some other cell systems besides the immunologically active cells. These drugs are also known to lower the resistance to some intercurrent infections. Due to these undesired side effects some naturally occurring factors are introduced into the therapy. These are e.g., TGF-beta, or some interleukins (IL-10 etc.). In our department and immunosuppressively acting substance was isolated from DHL which had the ability to inhibit the AA (adjuvant arthritis) in rats. In humans this SF (suppressive factor) stimulates the CD 8+ cells which are known to have suppressoric activity. This SF was successfully applied in some autoaggressive diseases, e.g., atopic eczema, multiple sclerosis, some polyradiculoenuritis, amyotropic lateral sclerosis etc. In this paper the results in the ALS patients are given. Amongst other possibilities of the therapy the application of antilymphocyte sera, monoclonal antibodies to some CD markers of lymphocytes and some methods of hyposensitizations of tolerance induction are mentioned. Further, an original method using antigen bound to isosoluble carrier is described. This administration of encephalitogen bound onto Sforon (polyacrylate spheres) sis not only inhibit the EAE manifestations but also enable the survival of guinea-pigs which had already manifested the clinical signs of EAE.

[Scintigraphic diagnosis of abscesses and other inflammatory processes using indium 111In labeled leukocytes]. / Scintigrafická diagnostika abscesu a jiných zánetlivých procesu indiem 111In znacenými leukocyty.

Autologous polymorphonuclear leucocytes are injected after separation and labelling with 111In oxine to the patient with a suspect inflammatory process and after 24 hours their localization is assessed by standard scintigraphic examination by a scintillation camera. The authors examined in a prospective investigation 33 patients--the sensitivity of the method was in that group 80%, the specificity 100%, the diagnostic accuracy 94%. The authors discuss the possibilities of application of the method in intraperitoneal abscesses and in some inflammations with another localization. They evaluate the contribution of the method in the diagnosis of inflammatory processes, as compared with the possibilities offered by computed tomography and ultrasound.