CN102204901A - Reagent and method for regulating immune molecules - Google Patents

Abstract

The present invention relates to agents and methods for modulating immune molecules. The present invention reveals for the first time that gabapentin is a substance useful for regulating immunity, which can inhibit some abnormally upregulated immune molecules. Thus providing a new target for clinical immune regulation.

Description

Reagents and methods for modulating immune molecules

technical field

The present invention is in the field of pharmacology; more particularly, the present invention relates to agents and methods for modulating immune molecules.

Background technique

Gabapentin (Gabapentin, GBP) is an antiepileptic drug, and foreign reports have good safety and therapeutic effect. In the 1990s, the Warner-Lambert company of the United States first successfully developed it, and it was first listed in the UK in 1993. my country successfully developed it in 2004, and the State Food and Drug Administration officially approved its production. In addition to its antiepileptic effect, gabapentin has been found clinically to have a significant effect on neuropathic pain, especially postherpetic neuralgia (PHN) and diabetic peripheral neuropathy (DPN). The study found that gabapentin has a unique effect on voltage-dependent Ca2 ⁺ channel currents in postsynaptic dorsal horn neurons, thus, gabapentin can interrupt the whole process leading to neuropathic pain, not just one of them links. Different animal pain models have shown that gabapentin has a good effect on neuropathic pain.

However, the mechanism of action of gabapentin is still unclear; and whether gabapentin has other functional effects has not been studied in depth.

Contents of the invention

It is an object of the present invention to provide reagents and methods for modulating immune molecules.

In the first aspect of the present invention, the use of gabapentin is provided for preparing a composition for regulating immunity.

In another preferred example, the regulation of immunity is regulation of α-βT cell receptor complex pathway.

In another preferred example, the regulation of immunity is to down-regulate the expression of immune-related genes: bone morphogenic protein-7 (Bmp7), complement component 3a receptor 1 (C3ar1), CD2 antigen (Cd2), CD37 antigen (Cd37) , CD3 antigen delta polypeptide (Cd3d), CD3 antigen g (Cd3g), CD3 antigen z (Cd3z), CD5 antigen (Cd5), CD6 antigen (Cd6), CD96 antigen (Cd96), complement factor B (Cfb), high affinity Neutral immunoglobulin γ Fc receptor I (Fcgr1), Fc receptor (Fcgrt), interleukin 2 receptor (Il2rb), killer cell hemagglutinin-like receptor subfamily A (Klra22), T cell receptor L20993, T Cell activation link protein (Lat), lymphocyte specific protein 1 (Lsp1), leukotriene B4 12-hydroxydehydrogenase (Ltb4dh), rat α-2-macroglobulin M84368, myosin IG (Myo1g), CD43 antigen Spn, T-cell receptor beta chain (Tcrb), tumor necrosis factor receptor superfamily Tnfrsf1b, tumor necrosis factor receptor superfamily Tnfrsf4, tumor necrosis factor receptor superfamily Tnfrsf5, tumor necrosis factor receptor superfamily Tnfsf10 or zeta-chain (TCR)-related protein kinase 70 (Zap70).

In another preferred example, the regulation of immunity is to reduce the rate of CD3 molecule positive cells.

In another preferred example, the CD3 molecule is a molecular marker of activated T cells, and its positive rate is abnormally increased or indicates immune hyperactivity.

In another preferred example, the composition is also used for inhibiting abnormally up-regulated immune molecules.

In another preferred embodiment, the composition is a drug.

In another aspect of the present invention, a method of regulating immunity is provided, the method comprising: administering an effective amount of gabapentin to a subject.

Other aspects of the invention will be apparent to those skilled in the art from the disclosure herein.

Description of drawings

Figure 1 shows the QRT-PCR verification of gene expression. in,

A is relative to the control group, the expression situation of the normal saline group improves the multiple;

B is relative to the normal saline group, the expression of the gabapentin group is increased by multiples.

The upper panel of Figure 2 shows the changes in protein levels verified by immunofluorescence. Among them, fluorescent dots represent CD3 positive cells.

The lower panel of Figure 2 shows the detection results of positive cells for CD3 molecules. Wherein, compared with the control group, ^*** p<0.001, Scale bar=50 μm.

Detailed ways

The research of the present inventor revealed for the first time that gabapentin is a substance useful for regulating immunity, and it can inhibit some abnormally up-regulated immune molecules.

gabapentin

Gabapentin (Gabapentin, GBP) is an antiepileptic drug, its chemical formula is 1-aminomethylcyclohexaneacetic acid, its molecular formula is C ₉ H ₁₇ NO ₂ , and its structural formula is shown in formula (I):

The gabapentin can be obtained through chemical synthesis.

The compounds of the present invention may be pharmaceutically acceptable salts, hydrates or precursors as long as they also have an immune-modulating effect. The "pharmaceutically acceptable salt" refers to a salt formed by reacting a class of compounds with inorganic acids, organic acids, alkali metals or alkaline earth metals. These salts include (but are not limited to): (1) salts formed with inorganic acids such as hydrochloric acid, sulfuric acid, nitric acid, phosphoric acid; (2) salts formed with organic acids such as acetic acid, oxalic acid, succinic acid, tartaric acid , methanesulfonic acid, maleic acid, or arginine. Other salts include those formed with alkali or alkaline earth metals such as sodium, potassium, calcium or magnesium, in the form of esters, carbamates, or other conventional "prodrugs".

The "precursor of the compound" refers to that the precursor of the compound undergoes metabolism or chemical reaction in the body of the patient and transforms into a compound represented by the structural formula (I) after being administered in an appropriate way.

The present invention also includes isomers and racemates of the above compounds, as long as they also have the effect of regulating immunity. Compounds possess one or more asymmetric centers. These compounds may thus exist as racemic mixtures, individual enantiomers, individual diastereoisomers, diastereomeric mixtures, cis or trans isomers.

use

The invention provides the use of gabapentin and its pharmaceutically acceptable salt for preparing the composition for regulating immunity.

The immune regulation includes: regulating the α-βT cell receptor complex pathway; or down-regulating the expression of immune-related genes: Bmp7, C3ar1, Cd2, Cd37, Cd3d, Cd3g, Cd3z, Cd5, Cd6, Cd96, Cfb, Fcgr1, Fcgrt, Il2rb, Klra22, L20993, Lat, Lsp1, Ltb4dh, M84368, Myo1g, Spn, Tcrb, Tnfrsf1b, Tnfrsf4, Tnfrsf5, Tnfsf10, or Zap70; or reduce the rate of cells positive for CD3 molecules.

The use of said gabapentin and its pharmaceutically acceptable salt also includes: inhibiting abnormally up-regulated immune molecules.

combination

As used herein, the term "composition of the present invention" includes pharmaceutical compositions and dietary supplements (such as nutraceutical compositions) as long as they contain gabapentin as an active ingredient for regulating immunity.

The present invention also provides a composition comprising: (a) an effective amount of gabapentin or a pharmaceutically acceptable salt thereof; and (b) a pharmaceutically acceptable carrier or excipient.

In the present invention, the term "comprising" means that various components can be used together in the mixture or composition of the present invention. Accordingly, the terms "consisting essentially of" and "consisting of" are included in the term "comprising".

In the present invention, a "pharmaceutically acceptable" ingredient is a substance suitable for use in humans and/or animals without undue adverse side effects (such as toxicity, irritation and allergic reactions), ie having a reasonable benefit/risk ratio.

In the present invention, "pharmaceutically acceptable carrier" is a pharmaceutically or food-acceptable solvent, suspending agent or solvent used to deliver gabapentin or a physiologically acceptable salt thereof to animals or humans. excipient. The carrier can be liquid or solid.

From the standpoint of ease of preparation and administration, preferred pharmaceutical compositions are solid compositions, especially tablets and solid-filled or liquid-filled capsules. Oral administration of the pharmaceutical composition is preferred.

The dosage form of the pharmaceutical composition of the present invention can be various, as long as it is the dosage form that can make the active ingredient reach the body of the mammal effectively. For example, it may be selected from: tablets, capsules, powders, granules, syrups, solutions, suspensions, or aerosols. Wherein gabapentin may exist in a suitable solid or liquid carrier or diluent.

The gabapentin and the composition thereof of the present invention may also be stored in a sterile device suitable for injection or infusion. Usually, in the pharmaceutical composition of the present invention, gabapentin as an active ingredient accounts for 0.1-50% (preferably 1-40%, more preferably 2-30%) of the total weight, and the rest is pharmaceutically acceptable carriers and other additives.

Mode of Administration and Dosage Form

The pharmaceutical composition of the present invention can be made into any conventional preparation form by conventional methods.

Generally, when the compounds or their pharmaceutically acceptable salts and compositions thereof are used for the above purposes, they can be mixed with one or more pharmaceutically acceptable carriers or excipients, such as solvents, diluents, etc. , and can be administered orally in the form of tablets, capsules, dispersible powders, granules or suspensions (containing e.g. about 0.05-5% suspending agent), syrups (containing e.g. about 10-50% sugar), and elixirs ( containing about 20-50% ethanol), or parenterally in the form of sterile injectable solutions or suspensions containing about 0.05-5% suspension in an isotonic medium. For example, these pharmaceutical formulations may contain from about 1 to 90%, usually from about 5 to 60%, by weight, of the active ingredient in admixture with a carrier.

The effective dose of active ingredient employed may vary with the compound employed, the mode of administration and the severity of the disease being treated. Generally, however, satisfactory results are obtained when the compounds of the present invention are administered at a dose of about 10-300 mg/kg of animal body weight per day, preferably in 1-3 divided doses per day, or in sustained release form. medication. For most large mammals, the total daily dose is about 5-3600 mg, preferably about 10-500 mg. Dosage forms suitable for internal administration contain about 1-200 mg of the active compound in intimate admixture with a solid or liquid pharmaceutically acceptable carrier. This dosage regimen can be adjusted to provide the optimum therapeutic response. For example, several divided doses may be administered daily or the dose may be proportionally reduced as the exigencies of the therapeutic situation dictate.

The compound or its pharmaceutically acceptable salt and its composition can be administered orally, intravenously, intramuscularly or subcutaneously; oral administration is preferred. Solid carriers include: starch, lactose, dicalcium phosphate, microcrystalline cellulose, sucrose, and kaolin, while liquid carriers include: sterile water, polyethylene glycol, nonionic surfactants, and edible oils (such as corn oil, peanut oil and sesame oil), as appropriate to the profile of the active ingredient and the particular mode of administration required. Adjuvants commonly used in the preparation of pharmaceutical compositions may also advantageously be included, such as flavourings, colours, preservatives and antioxidants such as vitamin E, vitamin C, BHT and BHA.

The active compounds or their pharmaceutically acceptable salts and compositions thereof can also be administered parenterally or intraperitoneally. Solutions or suspensions of these active compounds (as free base or pharmaceutically acceptable salts) can also be prepared in water suitably mixed with a surfactant, such as hydroxypropylcellulose. Dispersions can also be prepared in glycerol, liquid, polyethylene glycols, and mixtures thereof in oils. Under ordinary conditions of storage and use, these preparations contain a preservative to prevent the growth of microorganisms.

The pharmaceutical forms suitable for injection include: sterile aqueous solutions or dispersions and sterile powders (for the extemporaneous preparation of sterile injectable solutions or dispersion). In all cases, these forms must be sterile and must be fluid for easy syringe expulsion. Must be stable under the conditions of manufacture and storage and must be protected against the contaminating influence of microorganisms such as bacteria and fungi. The carrier can be a solvent or dispersion medium containing, for example, water, alcohols (such as glycerol, propylene glycol, and liquid polyethylene glycol), suitable mixtures thereof, and vegetable oils.

Gabapentin or its pharmaceutically acceptable salts and compositions thereof can also be administered in combination with other active ingredients or drugs.

When two or more drugs are administered in combination, the effect is generally better than that of the two drugs administered alone.

Preparation method of gabapentin and pharmaceutically acceptable salt thereof

Gabapentin can be prepared by methods known to those skilled in the art, such as chemical synthesis or extraction from plants. Preferably, a method for extracting gabapentin from plants can be used.

Below in conjunction with specific embodiment, further illustrate the present invention. It should be understood that these examples are only used to illustrate the present invention and are not intended to limit the scope of the present invention. The experimental methods not indicating specific conditions in the following examples are usually according to conventional conditions such as Sambrook et al., molecular cloning: the conditions described in the laboratory guide (New York: Cold Spring Harbor Laboratory Press, 1989), or according to the manufacturer's suggested conditions. Percentages and parts are by weight unless otherwise indicated.

Unless otherwise defined, all professional and scientific terms used herein have the same meanings as commonly understood by those skilled in the art. In addition, any methods and materials similar or equivalent to those described can also be applied in the present invention. The preferred implementation methods and materials described herein are for demonstration purposes only.

I. Materials and methods

Establishment and screening of animal models

SD rats: 220-250 g, male, provided by the Shanghai Experimental Animal Center of the Chinese Academy of Sciences, certificate number SCX (Shanghai) 2007-0005.

Surgical procedure:

1. Preliminary screening: stable for 2 to 3 days, and exclude rats with a pain threshold of less than 15 g (see below for the pain measurement method).

2. Surgery:

Surgical instruments: anesthetic (chloral hydrate 10%), normal saline, 1ml syringe, scalpel (handle + blade), 75% alcohol, ligature (6-0 silk), suture, tissue forceps, hemostat, ophthalmology Scissors, ophthalmic tweezers, tie tweezers, cotton balls, cotton swabs, suture needles, needle holders, spreaders.

a. Anesthesia: Weigh, record body weight, and inject 0.3ml/100g rats with 10% chloral hydrate intraperitoneally.

b. Taking the line connecting the two anterior superior iliac ridges of the rat as the midline, cut off the back hair of the rat, about 4 cm long and 2 cm wide, and use alcohol to remove the skin of the plucked area.

c. Use a scalpel to cut gently along the direction of the spine (with the anterior superior iliac spine as the midline), make a skin incision of 2 to 3 cm, and bluntly separate the muscles at a distance of about 2 mm from the spine.

d. Separate until a clear L6 transverse process appears in the visual field, break off the L6 transverse process and take it out.

e. After breaking off the L6 transverse process, two nerves can be clearly seen running side by side. The nerve near the spine is the L5 spinal nerve, and the other is the L4 spinal nerve. Carefully separate the L5 spinal nerve and pass the ligature through it with forceps And tie two knots, this process can not hurt the L4 spinal nerve (among them, the number L+ represents the lumbar first *).

f. Suture

3. Animals were bred for 7 days after surgery and administered.

Pain measurement method, model screening, behavioral measurement:

Pain measuring tool (von Frey filament) manufacturer: North Coast.

Cilia in grams: 2.7g, 3.9g, 5.0g, 6.9g, 10.8g, 15g, 20g.

Measuring method: Behavioral measurement was carried out from the third day to the seventh day after operation. Put the rats on a half-meter-high barbed wire and cover them with a brown (8×8×18cm) plastic box. After half an hour to one hour, the rats will be quieter and walk less. At this time, the pain measurement can be started. Use the cilia (filament) to pierce between the little finger and the ring finger of the left foot perpendicular to the surface of the rat's foot. The number of grams increases from small to large. pain threshold. If the pain threshold of the rat is less than 6.9 g after more than 3 days, the operation is considered successful.

Grouping situation:

Healthy rats without surgery were used as the control group; rats with successful models were randomly divided into 3 groups, pure surgery group, saline group, and drug administration group. The pure operation group (control group) was not treated; the administration group was given gabapentin at a dose of 150 mg/kg/d, and gabapentin was dissolved in normal saline; the saline group was given an equal volume of normal saline.

Microarray and PCR sample preparation

The rats were anesthetized and killed, and the L5 dorsal root ganglion (L5 refers to the lumbar 5 spinal nerve) was taken out within 10 minutes (the dorsal root ganglion is abbreviated as DRG), and quickly frozen in liquid nitrogen. The DRGs of 9 rats in each group were randomly divided into 3 biological repeats. Total RNA was extracted by Trizol method and purified by RNeasy (Qiagen, Hilden, Germany) kit.

Immunofluorescence sample preparation

Three rats in each group were anesthetized with 10% chloral hydrate and the dose was the same as above. Cut open the chest wall to fully expose the heart and descending aorta. The perfusion needle was inserted from the left apex, pushed forward to the descending aorta, and the hemostatic clamp was fixed. Inject 50ml of normal saline at 37°C to flush the circulating blood, and then inject 50ml of 37°C 4% PFA (4% paraformaldehyde, 0.2% picric acid, pH6.9). Immediately after that, 200ml of PFA at 4°C and 4% was pumped in for 5 minutes until the whole body of the rat was stiff. The L5 dorsal root ganglion was taken out, fixed in PFA at 4°C for 2.5 hours, and finally dehydrated with 10% sucrose solution for more than 24 hours, and then sliced.

Agilent chip hybridization and scanning

Take 100 pmol of total RNA extracted from each sample, and use the Quick Amp Labeling Kit One-Color kit (purchased with Agilent chips) for Cy3-labeled staining and amplification. The labeled cRNA was purified by RNeasy kit and quality controlled by NanoDrop ND-1000UV-VIS Spectrophotometer. After each group took 1.5 μg for fragmentation, they were loaded on 4×44K chips respectively, and hybridized overnight in a hybridization oven. 65°C, rotating speed 10rpm, and finally use Feature Extraction Software to scan the signal.

Real-time quantitative PCR (QRT-PCR)

Take 5 μg RNA from each group and mix with reverse transcriptase Superscript II and oligo(dT)18 for reverse transcription. Actin (Actin) cDNA was used as a quality control, and the primers for each gene were designed as shown in Table 1.

The PCR conditions were: 94°C for 5min, plus 32 cycles of denaturation-annealing-extension, wherein denaturation temperature was 94°C for 30s, annealing was at 58°C for 30s, and extension was at 72°C for 30s. Finally, 72°C for 5 minutes. This process is completed in ABI Power SYBR Green PCR Master Mix (ABI Company), and the operation is carried out in full accordance with the operation process provided by ABI Company.

Table 1

Immunofluorescence (direct method)

Antibody: FITC mouse anti-human CD3 monoclonal antibody was diluted 1:500 with light microscope diluent. Among them, the diluent for light microscopy is: 1×PBS containing 1% bovine serum albumin and 0.3% Triton X-100.

The fixed DRG was embedded in OCT (embedding agent, which is a water-soluble mixture of polyethylene glycol and polyvinyl alcohol), and sliced serially in a Microm HM 525 cryostat with a thickness of 14 μm. The sliced slices were taken every two slices, immersed in 0.01M PBS solution at room temperature for 15 minutes, and then the primary antibody was applied, overnight at 4°C, with a loading volume of 80 μl per slice. After that, soak and wash with 0.01M PBS solution for 5min×3 times, drop into the mounting solution to seal the slide, and observe under the confocal microscope.

data analysis

Comparisons between multiple groups were performed using one-way ANOVA and Tukey's HSD test. A significant difference was considered when the P value was <0.05. After importing the raw data obtained by chip scanning into Genespring GX 9.0, the points with signal saturation and insufficient signal are first screened out; effective signal points are subjected to Quartile standardization. Afterwards, double-standard difference screening between groups was carried out: 1. Tukey’s HSD test P value lower than 0.05; 2. Fold change >= 1.5. The screened differential genes were imported into Genmapp2.0 for pathway analysis.

For the results of immunofluorescence, a total of 6 slices were taken, and there were 3 animals in each group, and the positive cell rate was counted double-blindly. One person counted the total number of neurons, the other counted the number of positive cells (only those with clear nuclei were counted), and finally calculated the positive rates of each group to compare the differences.

II. Example

Example 1. Chip results show that gabapentin can reverse the level of some abnormally expressed immune molecule genes

In the one way ANONA test, a total of 9764 probes showed differences between groups (P<0.05). Among them, after the Tukey's HSD test, there were 7673 probes that were different between the saline group and the control group, while only 267 probes were different between the saline group and the pure surgery group, and the multiple comparison was >1.5. Since most of the genes represented by these 267 probes are predicted genes or their functions are not related to pain sensation, in subsequent studies, the inventors ignored the difference caused by normal saline, and directly compared the saline group with the administration group. After the above-mentioned double-standard screening, 479 probes were screened out from the saline group and the administration group, and all 479 probes were included in the above-mentioned 7673 probes. Excluding some genes whose functions have not been thoroughly studied and predicted genes, the inventors selected a total of 238 probes, including 20 receptor genes, 14 ion channels, 27 immune molecules (Table 2) and some synaptic proteins etc., some of which have been reported in previous studies.

Pathway analysis with Genmapp2.0 showed that in terms of immunology, the α-βT cell receptor complex pathway was significantly changed (P<0.001).

Table 2

A_44_P533794 1.74 down Tnfrsf1b Tumor necrosis factor receptor superfamily A_42_P552004 1.87 down Tnfrsf4 Tumor necrosis factor receptor superfamily A_42_P666951 1.70 down Tnfrsf5 Tumor necrosis factor receptor superfamily A_42_P733671 2.00 down Tnfsf10 Tumor necrosis factor receptor superfamily A_44_P994692 2.29 down Zap70 Zeta-chain (TCR)-related protein kinase 70 (Zap70)

Embodiment 2, QRT-PCR verification

The inventor randomly selected 13 probes from the above 238 probes for QRT-PCR verification, including 4 probes of immune molecules.

As a result, the change in expression was consistent with the chip results, as shown in Figure 1.

Embodiment 3, immunofluorescence verification

In addition to the gene level, the inventors hope to further confirm whether the protein level is also changed by immunofluorescence, as shown in the upper panel of FIG. 2 .

The present inventor compared the positive cell rate of CD3 molecules (CD3 molecule positive indicates activated T cells, and abnormal increase indicates immune hyperactivity). The rate returned to the normal level, and there was no difference with the control group, as shown in the lower figure of Figure 2.

discuss

The role of the immune system in the development of neuralgia has long been discovered. It has been confirmed that the cell bodies and fibers of neurons can be regulated by activated immune cells and immune cell-like glial cells. Therefore, the process of immune activation may play an important role in the occurrence and persistence of neuralgia. In the research of the present inventors, it was found that in rats after SNL surgery, some immune molecule genes in the dorsal root ganglia were significantly up-regulated, but 27 genes were down-regulated to normal or near-normal levels after administration. Pathway analysis also revealed significant alterations in the α-β T cell receptor complex pathway. Based on this, the inventors predicted that in the analgesic effect of gabapentin, there may be a mechanism for inhibiting T cell activation: T cells that enter the normal nervous system will withdraw by themselves because they cannot find a suitable antigenic epitope. Therefore, Positive cells were rarely seen in the control group. However, in the non-control group, once the T cells have determined the antigenic epitope, they will stay there and release a series of cytokines, such as interleukin-2, tumor necrosis factor and interferon. These factors can stimulate Schwann cells, macrophages, etc. to release more cytokines, such as pro-inflammatory cytokines and RO. The role of these cytokines in nervous system autoimmune diseases has been confirmed. In addition, they can sensitize TRPV1 receptors through cross-sensitization, thereby changing the sensitivity of neuronal receptors, and in this way play a role in the occurrence of hyperalgesia. effect. Therefore, the present inventors predicted that there is a mechanism of inhibiting T cell activation during the analgesic process of gabapentin.

All documents mentioned in this application are incorporated by reference in this application as if each were individually incorporated by reference. In addition, it should be understood that after reading the above teaching content of the present invention, those skilled in the art can make various changes or modifications to the present invention, and these equivalent forms also fall within the scope defined by the appended claims of the present application.

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Claims (8)

1. The use of gabapentin for preparing a composition for regulating immunity. 2. The use according to claim 1, characterized in that the regulation of immunity is the regulation of α-βT cell receptor complex pathway. 3. The use according to claim 1, characterized in that the immune regulation is to down-regulate the expression of immune-related genes: bone morphogenic protein-7, complement component 3a receptor 1, CD2 antigen, CD37 antigen, CD3 antigen δ Peptide, CD3 antigen g, CD3 antigen z, CD5 antigen, CD6 antigen, CD96 antigen, complement factor B, high affinity immunoglobulin gamma Fc receptor I, Fc receptor, interleukin 2 receptor, killer cell hemagglutinin-like Receptor subfamily A, T cell receptor L20993, T cell activation linker protein, lymphocyte specific protein 1, leukotriene B4 12-hydroxydehydrogenase, rat α-2-macroglobulin M84368, myosin IG , CD43 antigen Spn, T-cell receptor beta chain, tumor necrosis factor receptor superfamily Tnfrsf1b, tumor necrosis factor receptor superfamily Tnfrsf4, tumor necrosis factor receptor superfamily Tnfrsf5, tumor necrosis factor receptor superfamily Tnfsf10 or ζ -chain-associated protein kinase 70. 4. The use according to claim 1, characterized in that said regulation of immunity is to reduce the rate of positive cells of CD3 molecule. 5. The use according to claim 4, wherein said CD3 is a molecular marker of activated T cells, and its positive rate is abnormally increased or indicates immune hyperactivity. 6. The use according to claim 1, wherein said composition is also used for inhibiting abnormally up-regulated immune molecules. 7. The use according to claim 1, wherein said composition is a medicine. 8. A method for regulating immunity, characterized in that the method comprises: administering an effective amount of gabapentin to a subject.

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