CZ20012519A3 - Nucleoside intended for use as a medicament for treating immunity system response in exposition - Google Patents

Abstract

The response of an immune system to a challenge is modified by presenting the system with a nucleoside in a concentration selected to have an effect on a B7 marker that is inverse from the effect of the challenge. Contemplated challenges include allergens, neoplasm, virus, bacteria, infestation, and autoimmune reaction. Molecular markers of particular interest are B7-1 and B7-2. Preferred nucleosides are Ribavirin and Ribavirin analogs, especially provided within a concentration range between about 0.2 :M and about 5 :M, respectively, in a fluid containing cells expressing the B7 marker.

Description

(57)

A nucleoside for use as a medicament for treating an immune system response in an exposure correlating with an effect on a B7 marker, wherein the nucleoside is in an effective amount of a B7 molecular marker that acts opposite to the effect of the exposure. The exposure was selected from the group consisting of allergen, microorganism, neoplasm, challenge and autoimmune response, wherein the molecular marker is R7-1 and the nucleoside is not ribavirin. Preferred nucleosides are ribavirin and ribavirin analogs that are in a liquid containing cells expressing marker B7 in a concentration range of about 0.2 M to 5 M.

-22 7'7 · Μ · 999 9 9 • 999 9 9 9 9 9 9 9 9 9 9 9 9 ··· 999 99 999 999999

Nucleoside for use as a medicament for treating the immune system response in exposure

Technical field

The field of the invention is the field of immunology.

BACKGROUND OF THE INVENTION

In addition to commonly used physiological and phenotypic diagnostic parameters, sometimes diseases can be compared to each other based on molecular markers such as polids, mutations of specific genes, expression of certain cell surface markers, etc. Many of these markers act as a predictor or indicator of disease and can be used as diagnostic tool for clear definition of physiological conditions.

At present, a complex of diseases such as autoimmunity, asthma, cancer, etc. is being compared with specific molecular markers. Several studies have shown that there is a direct or indirect effect of the B7-1 and B7-2 co-stimulatory molecules on immune system modulation in diseases. However, despite such studies providing a detailed insight into the different expression levels of B7-1 and B7-2 in different diseases, there was no overall and consistent picture (Hepatology 25, No.5, 1997 pl108-1114). : Expression of costimulatory molecules B7-1 and B7-2 and human hepatocellular carcinoma, J. Cancer Res Clin Oncol 124, No. 7, 1998 p383-388, Expression of costimulatory molecules B71 and B7-2 on human gastric carcinoma J. Neuroimmunol., 84,

No.2, 1998 p179-187: Costimulatory CD80 (B7-1) and CD86 (B7-2) on cerebrospinal fluid cells in multiple sclerosis, J. Neuroimmunol 91, Nol-2, 1998, p198-203: B7-1 ( CD80), B72 (CD86), interleukin-13 and transforming growth factor-beta

9 9 RNA β m RNA RNA RNA RNA RNA RNA) 9 mRNA expression in CSF and peripheral blood mononuclear cells from multiple sclerosis patients).

In many cases, an apparent non-uniform relationship between B7-1, B7-2, and a specific disease can be observed, as shown in Figure 1. For example, in some types of malignancy, B7-1 is present in relatively high amounts and B7-2 is present in relatively small amounts. In other types of malignancies, B7-1 and B7-2 are in a completely opposite relationship (J. Cancer Res. Clin. Oncol. 124, No.7 1998 p383-388: Expression of costimulatory molecules B7-1 and B7- 2 on human gastric carcinoma, Br. J. Haematol 102, No. 5, 1998 pl257-1262: The expression of costimulatory molecules and their relationship to the prognosis of human acute myeloid leukemia: poor prognosis of B7-2-positive leukemia, Int. Mol. Med., 2, No.2, 1998 p177-171: Lack B7-1 and B7-2 on head and neck cancer cells and possible significance for gene therapy).

Expression of B7-1 and B7-2 also shows a non-uniform correlation with known cytokine patterns, as shown in FIG.

2. For example, overexpression of B7-1 is associated with positive and negative type 1 response regulation, and B7-2 expression is also related to positive and negative type 1 response regulation. The same can be said for B7-1 and B7-2. with type 2 response, as shown in Figure 1 (Am. J. Respir. Cell. Mol. Biol. 17, No.2, 1997 p235-242: Differential regulation of human, antigenspecific Type 1 and Type 2 responses by the B-7 homologues CD80 and CD86, J. Immunol. 156, No.8, 1996 p2387-2391: Costimulation of IL-4 production by murine B7-1 and B7-2 molecules).

It is still unclear which drugs or even which category of drugs will be effective in modulating B7-1 or B7-2 activity, and even if such drugs are identified, it is unclear how to advantageously use these co-stimulatory molecules to modulate the immune system. When all the unknowns are put together, there is still a need to provide methods and means suitable for modulating one or more B7 markers, particularly a method of affecting the immune system's response to a given exposure.

SUMMARY OF THE INVENTION

The invention discloses methods and compositions for a nucleoside for use as a medicament for treating an immune system response in exposure correlating to an effect on a B7 marker, wherein the nucleoside is in an effective amount of a molecular marker B7 that acts opposite to the effect of exposure.

Generally, the response is modified so that the system comes into contact with the nucleoside at a concentration selected to have an effect on the B7 marker, which acts opposite to the immunization effect. In one preferred embodiment of the invention, the immunization means is selected from the group consisting of allergens, neoplasm, virus, bacteria, attack and autoimmune response. Particularly interesting molecular markers are B7-1 and B7-2. In another preferred embodiment of the invention the nucleoside is a ribavirin analog and in a particularly preferred embodiment the nucleoside is ribavirin. In another preferred embodiment of the invention, sufficient nucleoside must be provided to achieve a concentration range in the liquid containing cells expressing marker B7 of about 0.2 M to 5 M.

In preferred embodiments of the invention, the immunization is associated with an enhanced Type 2 response and the administration of the nucleoside is related to the attenuation of the Type 2 response.

The invention discloses that there is a surprising connection between certain nucleosides, particularly ribavirin and its analogs, and the expression of one or more B7 markers. Further research revealed another unexpected link that the administration of such nucleosides can positively affect disease termination or other changes. In particular, a method has been investigated to modulate the immune system's response to exposure comprising (a) exposure correlating with effect on the B7 marker, (b) applying a nucleoside in a concentration range correlating with modulation of the molecular B7 marker that counteracts immunization; nucleoside

Term within a given concentration range.

"Nucleoside" means a compound containing any pentose or modified portion of pentose trapped at a specific position of the heterocycle or at the natural position of purine (position 9) or pyrimidine (position

1) or in an equivalent position on an analogue which particularly comprises

D- and L-forms of nitrogenous bicyclic and monocyclic heterocycles. The term "D-nucleosides" refers to nucleoside compounds having a sugar portion of D-ribose (e.g., adenosine).

The term "nucleosides" means nucleoside compounds having the sugar component of L-ribose.

The term "nucleotide" means nucleosides in which phosphoric acid esters have substituted the 5 'position of the nucleoside.

The term "pharmaceutically acceptable salt" means any salt obtained from inorganic or organic acids or bases.

The term " neoplasm " means any kind of autonomous disease growth of a tissue, which may or may not become malignant, including all types of cancer.

The term "treating and" treating a disease means performing a protocol, which may include administering one or more kinds of drugs to a patient to alleviate the symptoms or symptoms of the disease.

Such "treatment or" treatment does not require complete alleviation of the symptoms specifically includes or symptoms, does not require cure and protocols that have only a marginal effect on the patient (such as a placebo effect).

The term "immune system" means any collection of immunocompetent cells that collectively identify and attack foreign entities and that respond dynamically to new pathogens or other exposures. Examples of immune systems are the human or other mammalian immune system, which includes spleen, thymus B cells, T cells and antibodies.

• Defined here, must have cellular need not have humoral components, includes humoral component, can

The immune system as a component but may have or if the immune system include soluble cell molecules that contain antibodies or soluble molecules are

By this definition, platelets include cells, whole blood, and erythrocytes secreted from immunocompetent interleukins. Examples of IgG, IgM, IgE or IL2, IL4, IL10.

It is believed that the immune system also has blood depleted of fibrinogen, the blood because it contains immunocompetent which are capable of responding dynamically to the immune systems are media of immunocompetent cells. On the contrary, pathogens. Other cultures containing antibody solutions are not considered immune to the novel cell buffered system because they contain a large number of immunocompetent preferred embodiments of the invention by humans or other immune systems as defined herein.

The term "exposure" means any component or phenomenon that elicits an immune system response. Exposures can be divided into three categories: self exposures, stepchildren and cells.

animals

In the next, include the changed own exposure. Self-exposures include cells or molecules wherein the immune system and exposure components are from the same organism, self-proteins or autologous proteins, or fragments thereof. Examples include human blood cells, undifferentiated cells, antibodies or coagulation factors of the same human. Inadequate type of exposure to viruses or molecules, exposure components derived from exposure is xenogenic. a non-identical donor originating from the cells,

Examples of the bacterium, the type where the immune system and from different organisms include organs or viruses or any or cells of the type typical of other species, and include endotoxins, enzymes or structural proteins. Altered intrinsic exposure to molecules that are components of components include cells or molecules where the immune system and exposure originate from the same organism but where the exposure is subject to modification, degradation or

neoplastic changes. Examples of such modifications include modification of the B7 marker profile to antigen-expressing cells. Examples of degradation changes include cells intended for apoptosis or necrotic tissue. Examples of neoplastic changes indicate malignancy.

The terms "immune system response" and "immune response" mean any immune system response to an exposure. Of interest are immune responses that involve modulation of the B7 marker. Such modulation may include any combination of upregulation or downregulation of B7-1 and B7-2 expression. Thus, all responses listed in the tables of Figures 1 and 2 are examples of the immune system contemplated.

Other predicted immune system responses include the association of cellular components in cell-specific interactions or changes in genetic activity. Cell-specific interactions can be cell-cell interactions or cell-cell exposure components. Examples of cell-cell interactions are T cells that are in contact with T-helper cells or T-helper cells are in contact with macrophages. Examples of cell-exposure component interactions are antigen presenting cells that contain the exposure component, process the exposure component and express the processed exposure component on the cell surface or B-cells expressing the exposure component specific antibodies on their surface and bind the exposure components to the antibody. Changes in genetic activity may result from a refolding of genomic DNA or by selective activation of genes. Examples of refolding of genomic DNA are splicing leading to affinity maturation of antibodies against exposure or splicing leading to switching of classes between individual classes of antibodies. Examples of selective gene activation are enhancement or attenuation of the transcription or translation of genes that code for interleukins or B7-1 or B7-2.

The production of an effect of B7 that acts "opposite to the pattern associated with exposure means that the effect of B7 * 9 · 9 · 9 9 · 9 · 9 9 9 9 · · · · ···· · * Produced by the nucleoside itself acts at least partially in the opposite direction to that of exposure alone. Thus, when exposure is associated with reduced expression of B7-1, then the effect of B7 is where B7-1 can be at least partially evaluated. Similarly, if exposure is associated with enhanced expression of B72, the opposite effect of B7 is that in which B7-2 is at least partially reduced.

The term "immune system is in contact with the nucleoside" means that the nucleoside is sufficiently in contact with any component of the immune system to produce an immune system response. In preferred embodiments, this involves introducing the nucleoside into the body. In other embodiments, this involves introducing a nucleoside into a vein or other site of the immune system.

The term "immune system in contact with the nucleoside is broad enough to include any combination of in vivo, in vitro, or ex-vivo contact." In vivo contact may include injection, ingestion, transdermal delivery or inhalation. Examples of different types of injections are into muscle, intravenous or subcutaneous. Examples of various forms suitable for ingestion are tablets, syrups or powders. Occlusion dressings, ointments or electrophoretic methods by which transdermal delivery can be performed. Inhalation may be accompanied by evaporation and spraying methods.

In vitro contact can be accomplished either by introducing a solution containing the nucleoside into the immune system in a suitable composition, or by dissolving the nucleoside in a solution, which may be in or part of the immune system. Examples of delivery include automatic or manual pipetting, dripping or injection of solutions. Alternatively, the nucleoside may also be dissolved in a liquid by pouring ribavirin into the liquid and mixing. This solution may contain the immune system or there may be a carrier solution that includes a buffer, isotonic

solutions, blood. These carriers are then introduced into the immune system.

Ex-vivo contact can be achieved in several steps (1) obtaining parts of the immune system from the source, (2) applying the nucleoside to the immune system, and (3) at least partially returning the immune system to the source. Obtaining parts of the immune system can be accomplished by removing part of the immune system from an in vivo and in vitro source. Examples of in vivo sources are vertebrates that include humans and others that are not vertebrates. Returning to the system can be done by venipuncture, eye drip or puncture. Examples of in vitro sources are cell cultures that are contained in a cellular system, conditioned or stored blood. Return to the system can be accomplished by any liquid transfer method, for example, by automatic or manual pipetting, aspiration, dripping, etc. The return of the immune system to the source can be accomplished by any liquid transfer method. This can occur in the case of an in-vitro source by automatic or manual pipetting, aspiration, dripping, or in the case of an in vivo source by intravenous injection.

The nucleosides under consideration are ribavirin (Ι-β-D-ribofuranosyl-

-1,2,4-triazole-3-carboxamide) and any of its ribavirin derivatives are more one or non-hydroxyl hydrogen, lower, alkyl, alkylalkenyl, halogen analogs.

ribavirin,

Analogs wherein (1) hydroxyls which have less lower uryl, etc.

groups of than 25 is atoms.

replaced by lower and independently one aralkyl or more

Includes lower hydrogen parts, alkyl, etc.

which lower contains less aryl, lower aralkyl than 25 other nucleosides with or substituted with non-hydrogen atoms including OH, lower lower alkylalkenyl, halogen

Ribavirin, a ribavirin analogue, is preferably prepared in a buffered aqueous solution. However, in other embodiments of the invention, the nucleoside may be prepared into a variety of other liquids or solid forms. The liquid forms may be solutions containing only a solvent including water, DMSO or ethanol. Liquid forms may also contain solutions containing solvent mixtures or dissolved solids including water-ethanol mixtures, water-DMSO mixtures, buffers. Further, the liquid forms of the nucleosides may be mixed with, for example, a substance which modifies the consistency to form a gel, cream or ointment. Examples are amphiphilic molecules, waxes or gelatin. Solid forms may contain solids, which may or may not be the active ingredients. Examples of active ingredients are buffers, ion exchange resins, including MOPS, phosphates or citrates. Examples of inactive ingredients include starch, cellulose or silica. Further, solid forms may be included in various formulations, such as tablets, capsules, powder, etc.

In a preferred embodiment of the invention, sufficient nucleoside is prepared to achieve a concentration range of 0.2 M to 5 M in a liquid containing cells expressing marker B7. Concentrations of less preferred embodiments of the invention assume other concentrations in the range of 0.1 μΜ to 10 μΜ.

In preferred embodiments of the invention, the exposure correlates with an enhancement of the type 2 response, and the application of nucleosides correlates with a decrease in the type 2 response.

Mammalian immune systems contain two major classes of lymphocytes: B lymphocytes (B cells) that originate from the bone marrow and T lymphocytes (T cells) that originate from the thymus. B cells are responsible for humoral immunity (i.e., antibody production), while T cells are responsible for cell-mediated immunity. T cells are considered to fall into two subclasses. They are helper T cells and cytotoxic T cells. Helper T cells activate other lymphocytes including B cells and cytotoxic T cells and macrophages by releasing soluble protein mediators called cytokines that are involved in cell-mediated immunity. Lymphokines are a subset of cytokines.

It is contemplated that helper T cells generally fall into two subclasses. It is type 1 and type 2. Cells of type 1 (also known as Th1 cells) produce interleukin 2 (IL-2), tumor necrosis factor (TNFα) and interferon gamma (IFNγ) and are primarily responsible for cell-mediated immunity such as delayed type of hypersensitivity and antiviral immunity. In contrast, type 2 cells (also known as Th2 cells) produce interleukins IL4, IL-5, IL-6, IL-9, IL-10 and IL-13 and are primarily involved in assisting a humoral immune response, such as an allergen response, for example, IgE and IgG4 antibody rearrangements (Mosmann, 1989, Annu Rev Immunol, 7: 145-173).

The terms "type 1 and type 2 responses" include the full range of effects that result from the induction of type 1 and type lymphocytes

2. Among other such responses include variations in the production of the corresponding cytokines through transcription, translation, secretion, and probably other mechanisms, enhanced proliferation of the corresponding lymphocytes, and other effects associated with increased cytokine production that include effects on motility.

Type 1 and 2 responses can be selectively suppressed while others are either induced or remain unaffected, or type 1 or 2 responses can be selectively induced while other responses are suppressed or remain relatively unaffected. Certain nucleosides, such as ribavirin, are effective in selectively modulating the type 1 and 2 responses. Determining which nucleosides are effective in reducing the type 2 response is readily accomplished by experiment.

It is contemplated that the methods described herein may be used in the treatment of various diseases and, in fact, may be any diseases that respond well to said treatment. Among other things, it is contemplated that such combinations may be used to treat allergies, malignancies, viral infections, bacterial infections, or autoimmune diseases.

9 9 9 9 9 9 9 ♦ ♦ · · 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9

Infections treatable with nucleosides of the invention may be caused by respiratory syncytial virus (RSV), hepatitis B virus (HBV), hepatitis C virus (HCV), herpes simplex virus types 1 and 2, herpes genitalis, herpes keratitis, herpes encephalitis, herpes zoster, HIV , influenza A virus, hanntan virus (hemorrhagic fever), human papillomavirus (HPV), measles virus and fungi. In particular, it is contemplated that the combinations described herein can be used in the treatment of chronic viral and bacterial infections, including HIV, tuberculosis, leprosy, etc..

Infections that can be treated with the nucleosides of the invention include attack by intracellular protozoa such as helminth and attack by other parasites. Again, it is contemplated that the combinations described herein may be used in the treatment of chronic attack.

Tumors that can be treated are caused by viruses, and the effect may include inhibiting the transformation of cells infected with the virus to a neoplastic stage, inhibiting the spread of the virus from the transformed cells to normal cells and / or arresting the growth of the cells transformed with the virus.

Allergies believed to be treatable include all IgE and IgG allergies, hyper IgE syndrome, and skin conditions such as atopic dermatitis. It is also contemplated that said methods can be used in the treatment of transplant rejection (graft versus host) and response to the implant.

Autoimmune diseases can be classified as organ-specific diseases and non-organ-specific diseases. Non-organ autoimmune disease includes rheumatoid arthritis, gout and gout arthritis, systemic lupus erythematosus (SLE), Sjogren's syndrome, scleroderma, polymyositis and dermomyositis, ankylosing spondylitis and rheumatic fever. Organ-specific autoimmune disease is known to each organ and includes diabetes, thyroid disease (Grav's disease and Hashimoto's thyroitis), Addison's disease, and some kidney and lung diseases including allergy and

asthma, multiple sclerosis, myasthenia gravis, uveitis, psoriasis, forms of hepatitis and cirrhosis, abdominal cavity diseases, inflammatory bowel diseases and some types of female and male infertility. Autoimmune processes can also be stimulated by viral infections, which include HIV, may be the result of transplant rejection, and may accompany certain tumors, or may be due to the action of certain chemicals.

Synthesis

The synthesis of ribavirin is well known and the synthesis of ribavirin analogs is contemplated.

Application

It is contemplated that the nucleosides of the invention may be administered in any suitable pharmaceutical composition and according to any suitable protocol. Preferred dosages and protocols were compiled based on the results of experiments in certain patients. Such experiments need not be extensive, and nucleosides are expected to be administered to humans at a dose of 100 mg / day and about 5,000 mg / day. In humans and other systems, ribavirin or other nucleoside is believed to meet parameters such as nucleoside concentration in a liquid containing cells expressing B7 of about 2M to 5M.

Of course, one skilled in the art will appreciate that in treating a disease, the therapeutically effective amount varies according to the infection depending on the condition of the disease being treated, its severity, the treatment regimen, the kinetics of the pharmaceutical compositions, and the patient being treated (whether animal or human). Effective doses may range from 1 mg / kg or less to 25 mg / kg of body weight or more. Generally, the therapeutically effective amount of the second pharmaceutical composition ranges from a little less than 1 mg / kg to 25 mg / kg of the patient's body weight, depending on the nucleosides used, the condition and the infection being treated and the mode of administration. This dose range generally produces an effective blood concentration of active nucleosides that is in the range of 0.04 to 100 micrograms / cc of the patient's blood. However, it is believed that it is possible to develop treatment regimens suitable for the patient by administering a small amount and then increasing the amount until the side effect becomes undesirable or the desired effect is achieved.

The administration of the nucleoside of the invention may take place orally, parenterally (by subcutaneous injection, intravenous, intramuscular, intrasternal injection or infusion), spray inhalation or rectally, topically and so on. The dosage unit contains conventional non-toxic pharmaceutically acceptable carriers, adjuvants and vehicles.

It is contemplated that the nucleosides of the invention may be prepared in admixture with a pharmaceutically acceptable carrier. For example, the nucleosides of the invention may be administered orally as pharmaceutically acceptable salts. Since the nucleosides of the invention are mostly water-soluble, they can be administered intravenously in saline (e.g., pH adjusted to 7.2-7.5). Conventional buffers such as phosphates, carbonates or citrates may be used for this purpose. Of course, one skilled in the art can modify the compositions to provide a variety of compositions for certain modes of administration without the compositions of the invention becoming unstable or losing their therapeutic activity. In particular, treatment of nucleosides to render them more soluble in water or other carrier can be readily accomplished by a small treatment (salt formation, esterification, etc.) that is well known in the art. It is also well known to one skilled in the art how to adapt the route of administration and dosage regimen of certain nucleosides to optimize the kinetics of the putative nucleoside pharmaceutical composition in order to achieve the maximum benefit that is beneficial to the patient.

· 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 · · · ·· · <··

In certain pharmaceutical dosage forms, a nucleoside administered dosage form that particularly includes acylated (acetylated or other) derivatives, with pyridine esters and various nucleoside salt forms being preferred. One skilled in the art is able to recognize how necessary to modify the dosage forms to allow the introduction of active nucleosides into the target site in the host organism or patient. One of ordinary skill in the art can also utilize the advantageous pharmacokinetic parameters of the dosage forms when administering nucleosides to a target site of a host organism or patient to achieve maximum effect.

In addition, the putative nucleosides may be administered separately or together and separately administered in any manner. The amount of active ingredient and pharmaceutically active ingredient and the relative timing of administration are selected to achieve the desired therapeutic effect.

Methods of administering the putative nucleosides range from continuous administration (intravenous infusion) to daily oral administration (e.g., QID) and may include oral, topical, parenteral, intramuscular, intravenous, subcutaneous, transdermal (including enhancer penetration), buccal, and intravenous administration. suppositories.

Overview of the drawings

On Picture no. 1 Yippee table where are said specific diseases and their correlation with expression B7-1 and B7-2. On Picture no. 2 Yippee table where j sou said different types

diseases and their correlation with expression of type 1, type 2, B7-1 and B7-2.

DETAILED DESCRIPTION OF THE INVENTION

Example 1:

In the method of treatment of the invention, the therapeutically effective amount of the nucleoside is preferably admixed with a pharmaceutically acceptable carrier based on conventional pharmaceutical techniques to produce a suitable dose. The carrier may take various forms depending on the form of preparation desired for administration, for example oral or parenteral administration. In preparing the pharmaceutical compositions for oral pharmaceutical form, the usual pharmaceutical medium may be used. In the case of liquid oral forms such as suspensions, elixirs and solutions, suitable carriers, additives including water, glycols, oils, alcohols, preservatives, colorants and the like can be used. For oral administration, solid forms such as powder, preparation of tablets, capsules and suppositories, suitable carriers and additives including starches, sugar carriers such as dextrose, mannitol, lactose and lubricants, related carriers, diluents, granulating binders, disintegrating agents may be used. reagents and the like.

the agents, necessary tablets and capsules can be coated to form enteric-coated tablets and provide sustained release.

In the case of parenteral compositions, the carrier will usually comprise sterile water or aqueous sodium chloride solution and other ingredients which may, for example, form a dispersion. Of course, when sterile water is used and the individual components are sterile, the carriers are also sterilized. Suspensions for injection are also prepared, in which case appropriate liquid carriers, suspending agents and the like may be employed.

It is preferred that the active nucleosides of the invention be used to be relatively less toxic to host cells for which they are not intended and to have a relatively greater effect on their targets. In this regard, it may also be advantageous that Lnucleosides may exhibit higher stability as compared to Dnucleosides which lead to better pharmacokinetics. This can be achieved by the fact that L-nucleosides do not recognize enzymes and therefore have a longer half-life.

Thus, this method demonstrates that the use of ribavirin and other nucleosides advantageously modifies the molecular marker B7.

Claims (12)

PATENT CLAIMS A nucleoside for use as a medicament for the treatment of an immune system response in an exposure correlating with an effect on a B7 marker, wherein the nucleoside is in an effective amount of a B7 molecular marker that acts opposite to the effect of the exposure. contains allergen. The nucleoside of claim 1, wherein the exposure to m, 3. The nucleoside that the exposure of claim 1 comprises a neoplasm that The exposure nucleoside of claim 1 comprises a virus. m, denoting by, denoting by, denoting a reaction. of claims 1 to 8, wherein the molecular marker is 5. The nucleoside of claim 1, wherein the exposure comprises a bacterium. 6. The nucleoside of claim 1, wherein the exposure comprises an attack. 7. The nucleoside of claim 1, wherein the exposure comprises an autoimmune 8. A nucleoside according to any one of the following: B7-1. 9. Nucleoside according to any of claims 1 to 8, ..... .mu.Ci by that molecular the marker is B7-2. 10. Nucleoside according to any of the claims 1 to 8 v y z n a č u j that is nucleoside is ribavirin. 11. Nucleoside according to any of the claims 1 to 8 v y z n a č u j that is nucleoside is analog ribavirin. 12. The nucleoside of claim 1, wherein the exposure is selected from the group consisting of an allergen, a microorganism, a neoplasm, an attack and an autoimmune response, wherein the molecular marker is B7-1 and the nucleoside is ribavirin. 13. The nucleoside of claim 1, wherein the exposure is selected from the group consisting of allergen, microorganism, neoplasm, infestation and autoimmune response, wherein the molecular marker is B7-2 and the nucleoside is ribavirin. 14. The nucleoside of claim 1, wherein the exposure is selected from the group consisting of allergen, microrganism, neoplasm, infestation and autoimmune response, wherein the molecular marker is R7-1 and the nucleoside is not ribavirin. Nucleoside according to any one of claims 12 to 14, characterized in that the concentration range in the liquid containing cells expressing the B7 marker is approximately 0.2 M to 5 M. 16. The nucleoside of any one of claims 1 to 8, further comprising exposure correlating with a Type 2 response enhancement and applying a nucleoside correlating with a Type 2 response attenuation.