WO2024096261A1 - Composition for preventing or treating autoinflammatory diseases, and uses thereof - Google Patents

Abstract

The present invention relates to a pharmaceutical composition for treating or preventing autoinflammatory diseases, comprising, as an active ingredient, TLR inhibitor peptide 1 (TIP-1) or MAL/MyD88 inhibitory peptide 2 (MIP-2) or a polynucleotide(s) encoding same. It has been identified that the peptides inhibit inflammation in animal models with autoinflammatory diseases and can alleviate clinical symptoms, and thus the present invention can be used as a treatment agent and in a treatment method for autoinflammatory diseases.

Description

Composition for preventing or treating autoinflammatory diseases and uses thereof

The present invention provides a composition for preventing or treating autoinflammatory diseases and its use. More specifically, a composition for preventing or treating adult-onset Still's disease (AOSD) and a use thereof are provided.

Still's disease, one of the autoinflammatory diseases, is a systemic form of juvenile rheumatoid arthritis. It was first described by Still and is a disease whose cause has not yet been identified. It occurs in both children and adults. Adult-onset Still's disease, which develops in adults, has been reported all over the world since it was reported by Bywaters in 1971, and is known as a rare disease and a cause of unexplained fever.

Adult-onset Still's disease is generally reported to be a benign disease with a good prognosis, but fatal cases in which some patients have died from it have been reported, and if accompanied by hemophagocytosis syndrome, worsening liver function, infection, etc., the patient may die. It may reach a state of being. Domestic research results have also reported a prognosis of death in approximately 10% of patients with the disease.

A treatment for adult-onset Still's disease has not yet been clearly developed, and treatment development is still ongoing.

The object of the present invention is TIP-1 (TLR inhibitor peptide 1) or MIP-2 (MAL/MyD88 inhibitory peptide 2) peptide; The aim is to provide a pharmaceutical composition for the treatment or prevention of a) autoinflammatory disease or b) hypertrophy of the spleen or lymph nodes, comprising as an active ingredient a polynucleotide encoding the peptide.

Another object of the present invention is TIP-1 (TLR inhibitor peptide 1) or MIP-2 (MAL/MyD88 inhibitory peptide 2) peptide; The aim is to provide a health functional food composition for improving or preventing a) auto-inflammatory disease or b) enlargement of the spleen or lymph nodes, comprising as an active ingredient a polynucleotide encoding the peptide.

In order to achieve the above object, the present invention provides a TIP-1 (TLR inhibitor peptide 1) or MIP-2 (MAL/MyD88 inhibitory peptide 2) peptide; Or a polynucleotide encoding the peptide; provided is a pharmaceutical composition for treating or preventing auto-inflammatory diseases containing as an active ingredient.

In addition, the present invention provides a TIP-1 (TLR inhibitor peptide 1) or MIP-2 (MAL/MyD88 inhibitory peptide 2) peptide; Or a polynucleotide encoding the peptide; provided is a pharmaceutical composition for preventing or treating enlargement of the spleen or lymph nodes, comprising as an active ingredient.

Additionally, the present invention provides a TIP-1 (TLR inhibitor peptide 1) or MIP-2 (MAL/MyD88 inhibitory peptide 2) peptide; Or a polynucleotide encoding the peptide; provided is a health functional food composition for improving or preventing auto-inflammatory diseases containing as an active ingredient.

In addition, the present invention provides a TIP-1 (TLR inhibitor peptide 1) or MIP-2 (MAL/MyD88 inhibitory peptide 2) peptide; Or a polynucleotide encoding the peptide; provided as an active ingredient in a health functional food composition for improving or treating enlargement of the spleen or lymph nodes.

In addition, the present invention provides a method for preventing or treating autoinflammatory diseases comprising administering TIP-1 (TLR inhibitor peptide 1) or MIP-2 (MAL/MyD88 inhibitory peptide 2) to a subject in a therapeutically effective amount. to provide.

In addition, the present invention provides a method for preventing or treating spleen or lymph node enlargement, comprising administering TIP-1 (TLR inhibitor peptide 1) or MIP-2 (MAL/MyD88 inhibitory peptide 2) to a subject in a therapeutically effective amount. Provides a method.

Additionally, the present invention provides the use of TIP-1 (TLR inhibitor peptide 1) or MIP-2 (MAL/MyD88 inhibitory peptide 2) for the prevention or treatment of autoinflammatory diseases.

Additionally, the present invention provides the use of TIP-1 (TLR inhibitor peptide 1) or MIP-2 (MAL/MyD88 inhibitory peptide 2) for the prevention or treatment of spleen or lymph node enlargement.

In addition, the present invention provides the use of TIP-1 (TLR inhibitor peptide 1) or MIP-2 (MAL/MyD88 inhibitory peptide 2) for the manufacture of drugs for preventing or treating autoinflammatory diseases.

Additionally, the present invention provides the use of TIP-1 (TLR inhibitor peptide 1) or MIP-2 (MAL/MyD88 inhibitory peptide 2) for the manufacture of a drug for preventing or treating spleen or lymph node enlargement.

The present invention provides a TIP-1 (TLR inhibitor peptide 1) or MIP-2 (MAL/MyD88 inhibitory peptide 2) peptide; Or, it relates to a pharmaceutical composition for the treatment or prevention of auto-inflammatory diseases containing as an active ingredient a polynucleotide encoding the peptide, and it has been confirmed that it inhibits the activity against inflammation, so it can be used as an auto-inflammatory treatment and treatment method. .

Figure 1 shows a schematic diagram of the establishment and treatment process of an adult-onset Still's disease (AOSD) animal model.

Figure 2 shows changes in body temperature of interferon gamma (IFN-gamma; hereinafter referred to as IFN-γ) knockout mice through treatment with TIP-1 (TLR inhibitor peptide 1) or MIP-2 (MAL/MyD88 inhibitory peptide 2). Indicates confirmed data.

Figures 3 and 4 show data confirming the size of the spleen and lymph nodes of IFN-γ knockout mice through TIP-1 or MIP-2 treatment.

Figure 5 shows data confirming the level of activity of inflammatory cytokines IL-1β and IL-18 in the serum of AOSD model mice.

Figure 6 shows data confirming the inflammatory state of lymph node and spleen tissue through H&E (hematoxylin and eosin) staining.

Hereinafter, the present invention will be described in more detail.

The present invention provides a TIP-1 (TLR inhibitor peptide 1) or MIP-2 (MAL/MyD88 inhibitory peptide 2) peptide; Or a polynucleotide encoding the peptide; provided is a pharmaceutical composition for treating or preventing auto-inflammatory diseases containing as an active ingredient.

The TIP-1 (TLR inhibitor peptide 1) may be a peptide consisting of the amino acid sequence represented by SEQ ID NO: 1.

[SEQ ID NO: 1]

RQIKIWFQNRRMKWKKSHCRVLLI

The MIP-2 (MAL/MyD88 inhibitory peptide 2) may be a peptide consisting of the amino acid sequence represented by SEQ ID NO: 2.

[SEQ ID NO: 2]

RQIKIWFQNRRMKWKKPWCKYQMLQALT

The autoinflammatory disease may be Still's disease or adult-onset Still's disease (AOSD).

The pharmaceutical composition can inhibit the activity of IL-1β or IL-18.

The pharmaceutical composition can inhibit enlargement of the spleen or lymph nodes.

In addition, the present invention provides a TIP-1 (TLR inhibitor peptide 1) or MIP-2 (MAL/MyD88 inhibitory peptide 2) peptide; Or a polynucleotide encoding the peptide; provided is a pharmaceutical composition for preventing or treating enlargement of the spleen or lymph nodes, comprising as an active ingredient.

The pharmaceutical composition can inhibit enlargement of the spleen or lymph nodes caused by Still's disease or adult-onset Still's disease (AOSD).

In another embodiment of the present invention, the pharmaceutical composition may contain suitable carriers, excipients, disintegrants, sweeteners, coating agents, bulking agents, lubricants, lubricants, flavoring agents, antioxidants, buffers, bacteriostatic agents, etc. commonly used in the preparation of pharmaceutical compositions. It may further include one or more additives selected from the group consisting of diluents, dispersants, surfactants, binders, and lubricants.

Specifically, carriers, excipients, and diluents include lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, gum acacia, alginate, gelatin, calcium phosphate, calcium silicate, cellulose, methyl cellulose, and microcrystalline. Cellulose, polyvinyl pyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate, and mineral oil can be used. Solid preparations for oral administration include tablets, pills, powders, granules, and capsules. agents, etc., and such solid preparations can be prepared by mixing the composition with at least one or more excipients, such as starch, calcium carbonate, sucrose or lactose, gelatin, etc. In addition to simple excipients, lubricants such as magnesium styrate and talc can also be used. Liquid preparations for oral use include suspensions, oral solutions, emulsions, and syrups. In addition to the commonly used simple diluents such as water and liquid paraffin, various excipients such as wetting agents, sweeteners, fragrances, and preservatives may be included. Preparations for parenteral administration include sterilized aqueous solutions, non-aqueous solutions, suspensions, emulsions, freeze-dried preparations, suppositories, etc. Non-aqueous solvents and suspensions may include propylene glycol, polyethylene glycol, vegetable oil such as olive oil, and injectable ester such as ethyl oleate. As a base for suppositories, witepsol, macrogol, tween 61, cacao, laurin, glycerogeratin, etc. can be used.

According to one embodiment of the present invention, the pharmaceutical composition is intravenous, intraarterial, intraperitoneal, intramuscular, intraarterial, intraperitoneal, intrasternal, transdermal, intranasal, inhalational, topical, rectal, oral, intraocular or It can be administered to a subject in a conventional manner via the intradermal route.

The dosage of the active ingredient according to the present invention may vary depending on the subject's condition and weight, type and degree of disease, drug form, administration route and period, and may be appropriately selected by a person skilled in the art, and the daily dosage is 0.01 mg. /kg to 200 mg/kg, preferably 0.1 mg/kg to 200 mg/kg, more preferably 0.1 mg/kg to 100 mg/kg. Administration may be administered once a day or divided into several administrations, and the scope of the present invention is not limited thereby.

In addition, the present invention provides a TIP-1 (TLR inhibitor peptide 1) or MIP-2 (MAL/MyD88 inhibitory peptide 2) peptide; Or a polynucleotide encoding the peptide; provided is a health functional food composition for improving or preventing auto-inflammatory diseases containing as an active ingredient.

In addition, the present invention provides a TIP-1 (TLR inhibitor peptide 1) or MIP-2 (MAL/MyD88 inhibitory peptide 2) peptide; Or a polynucleotide encoding the peptide; provided as an active ingredient in a health functional food composition for improving or treating enlargement of the spleen or lymph nodes.

The health functional food includes various nutrients, vitamins, minerals (electrolytes), flavoring agents such as synthetic and natural flavors, colorants and thickening agents (cheese, chocolate, etc.), pectic acid and its salts, alginic acid and its salts, It may contain organic acids, protective colloidal thickeners, pH adjusters, stabilizers, preservatives, glycerin, alcohol, carbonating agents used in carbonated beverages, etc.

In addition, it may contain pulp for the production of natural fruit juice, synthetic fruit juice, and vegetable drinks. These ingredients can be used independently or in combination. In addition, the health functional food composition may be in the form of any one of meat, sausage, bread, chocolate, candy, snacks, confectionery, pizza, ramen, gum, ice cream, soup, beverages, tea, functional water, drink, alcohol, and vitamin complex. It can be.

In addition, the above-mentioned health functional food may additionally contain food additives, and its suitability as a “food additive” is determined according to the general provisions and general test methods of the Food Additive Code approved by the Food and Drug Administration, unless otherwise specified. Determination is made according to relevant standards and standards.

Items listed in the "Food Additives Code" include, for example, chemical compounds such as ketones, glycine, potassium citrate, nicotinic acid, and cinnamic acid, natural additives such as subchromic pigment, licorice extract, crystalline cellulose, cold pigment, and guar gum, L - Examples include mixed preparations such as sodium glutamate preparations, noodle-added alkaline preparations, preservative preparations, and tar color preparations.

At this time, in the process of manufacturing health functional foods, the content of the active ingredients added to the food can be appropriately adjusted as needed, and is preferably added in an amount of 1 to 90 parts by weight per 100 parts by weight of the food. .

In addition, the present invention provides a method for preventing or treating autoinflammatory diseases comprising administering TIP-1 (TLR inhibitor peptide 1) or MIP-2 (MAL/MyD88 inhibitory peptide 2) to a subject in a therapeutically effective amount. to provide.

In addition, the present invention provides a method for preventing or treating spleen or lymph node enlargement, comprising administering TIP-1 (TLR inhibitor peptide 1) or MIP-2 (MAL/MyD88 inhibitory peptide 2) to a subject in a therapeutically effective amount. Provides a method.

The therapeutically effective amount is an amount effective in treating a disease, such as an amount of the composition administered to the subject to be treated, preventing recurrence, alleviating symptoms, inhibiting direct or indirect pathological consequences, or It may include any amount of the composition that prevents metastasis, reduces the rate of progression, alleviates or temporarily alleviates the condition, or improves the prognosis. In other words, the therapeutically effective amount can be interpreted as encompassing all doses at which disease symptoms are improved or completely cured by the composition.

The subject may be a human or a non-human animal, and the non-human animals include vertebrates such as non-human primates, sheep, dogs, cats, rabbits and ferrets, rodents such as mice, rats and guinea pigs, birds such as chickens and May include, but is not limited to, pigeons, amphibians and reptiles. Preferably, the subject may be a mammal, and more preferably, the subject may be a human.

The administration refers to the administration of a substance (eg, TIP-1 or MIP-2) to achieve the purpose of treating the disease.

The prevention or treatment method of the present invention not only treats the disease itself before the symptoms appear, but also inhibits the symptoms by administering the TIP-1 (TLR inhibitor peptide 1) or MIP-2 (MAL/MyD88 inhibitory peptide 2). It also includes doing or avoiding. In the management of disease, the prophylactic or therapeutic dose of a particular active ingredient will vary depending on the nature and severity of the disease or condition and the route by which the active ingredient is administered. Dosage and frequency of dosage will vary depending on the age, weight, and response of the individual patient. A suitable dosage regimen can be easily selected by one of ordinary skill in the art taking these factors into account.

Additionally, the present invention provides the use of TIP-1 (TLR inhibitor peptide 1) or MIP-2 (MAL/MyD88 inhibitory peptide 2) for the prevention or treatment of autoinflammatory diseases.

Additionally, the present invention provides the use of TIP-1 (TLR inhibitor peptide 1) or MIP-2 (MAL/MyD88 inhibitory peptide 2) for the prevention or treatment of spleen or lymph node enlargement.

In addition, the present invention provides the use of TIP-1 (TLR inhibitor peptide 1) or MIP-2 (MAL/MyD88 inhibitory peptide 2) for the manufacture of drugs for preventing or treating autoinflammatory diseases.

Additionally, the present invention provides the use of TIP-1 (TLR inhibitor peptide 1) or MIP-2 (MAL/MyD88 inhibitory peptide 2) for the manufacture of a drug for preventing or treating spleen or lymph node enlargement.

The drug is prepared in unit dose form by formulating it using a pharmaceutically acceptable carrier according to a method that can be easily performed by a person skilled in the art to which the invention pertains, or by placing it in a multi-dose container. can be manufactured.

The pharmaceutically acceptable carriers are those commonly used in preparation, and include lactose, dextrose, sucrose, sorbitol, mannitol, starch, gum acacia, calcium phosphate, alginate, gelatin, calcium silicate, microcrystalline cellulose, Includes, but is not limited to, polyvinylpyrrolidone, cellulose, water, syrup, methyl cellulose, methyl hydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate, and mineral oil. In addition to the above ingredients, the pharmaceutical composition of the present invention may further include lubricants, wetting agents, sweeteners, flavoring agents, emulsifiers, suspending agents, preservatives, etc.

The content of additives included in the drug is not particularly limited and can be appropriately adjusted within the content range used in conventional formulations.

The medicine consists of injectable formulations such as aqueous solutions, suspensions, emulsions, etc., pills, capsules, granules, tablets, creams, gels, patches, sprays, ointments, warning agents, lotions, liniment agents, pasta agents, and cataplasma agents. It may be formulated in the form of one or more external preparations selected from the group.

The drug may contain additional pharmaceutically acceptable carriers and diluents for formulation. The pharmaceutically acceptable carriers and diluents include excipients such as starch, sugar, and mannitol, fillers and extenders such as calcium phosphate, cellulose derivatives such as carboxymethylcellulose, hydroxypropylcellulose, gelatin, alginate, and polyvinyl chloride. Including, but not limited to, binders such as rolidone, lubricants such as talc, calcium stearate, hydrogenated castor oil and polyethylene glycol, disintegrants such as povidone and crospovidone, and surfactants such as polysorbate, cetyl alcohol, and glycerol. No. The pharmaceutically acceptable carrier and diluent may be biologically and physiologically friendly to the subject. Examples of diluents include, but are not limited to, saline, aqueous buffers, solvents, and/or dispersion media.

Matters mentioned in the composition, treatment method and use of the present invention apply equally unless contradictory to each other.

Hereinafter, to aid understanding of the present invention, it will be described in detail through examples. However, the following examples are merely illustrative of the content of the present invention, and the scope of the present invention is not limited to the following examples. Examples of the present invention are provided to more completely explain the present invention to those with average knowledge in the art.

[Example 1] Preparation of TIP-1 and MIP-2 peptides

The TIP-1 (TLR inhibitor peptide 1) peptide used in this example consists of the amino acid sequence (RQIKIWFQNRRMKWKKSHCRVLLI) shown in SEQ ID NO: 1, and the MIP-2 (MAL/MyD88 inhibitory peptide 2) peptide is shown in SEQ ID NO: 2. It consists of an amino acid sequence (RQIKIWFQNRRMKWKKPWCKYQMLQALT). The TIP-1 peptide and the MIP-2 peptide were synthesized with 95 percent purity by Peptron Co., Ltd.

[Example 2] Effect of TIP-1 or MIP-2 treatment in AOSD (adult-onset Still's disease) animal model

To evaluate whether the TIP-1 peptide and MIP-2 peptide synthesized in Example 1 exhibit treatment and improvement effects on adult-onset Still's disease (AOSD), adult-onset Still's disease (AOSD) An animal model for onset Still's disease (AOSD) was established. In the experiment, IFN-γ Knockout (IFNγ KO) mice and normal C57BL/6J mice (wild type) purchased from Jackson Lab., USA, were used.

As shown in Figure 1, in order to establish an AOSD animal model, 1.5 mg/ml of Mycobacterium mixed Complete Freund's Adjuvant (CFA) was injected subcutaneously into the tail of the mouse on day 0 and week 2 of the experiment to develop AOSD ( adult-onset Still's disease) was induced. PBS (Phosphate-Buffered Saline) was administered to the control group of each mouse. TIP-1 or MIP-2 synthesized in Example 1 was intraperitoneally administered to mice in which AOSD was induced by CFA at a dose of 10 nmol/g (200 nmol/20g mice) every day for 4 weeks starting from the 3rd week. The body temperature and weight of the mice were examined every week from day 0 and week 2 of the experiment. After the mice were sacrificed at week 7, the lymph nodes and spleens were removed and their sizes were measured.

As shown in Figure 2, fever occurred due to inflammation in AOSD-induced IFN-γ knockout mice (IFN KO CFA), but injection of TIP-1 or MIP-2 peptide (IFN KO CFA+TIP or IFN KO CFA) caused fever due to inflammation. +MIP) was confirmed to have improved. At this time, it was confirmed that no special weight change occurred, indicating that there was no negative effect on viability and growth. In addition, as shown in Figures 3 and 4, the size of lymph nodes and spleen increased due to AOSD symptoms in AOSD-induced mice (CFA), but injection of TIP-1 or MIP-2 peptide ( It was confirmed that the size of the lymph nodes and spleen, which had been increased through CFA+TIP or CFA+MIP, decreased.

[Example 3] Measurement of IL-1β and IL-18 in serum

To evaluate whether the TIP-1 peptide and MIP-2 peptide synthesized in Example 1 exhibit a therapeutic and improvement effect on adult-onset Still's disease (AOSD), IL-1β, an inflammatory cytokine, and serum levels of IL-18 were measured. The levels of IL-1β and IL-18 in mouse serum were measured by ELISA (Enzyme-Linked Immunosorbent Assay). Blood samples extracted from each mouse were centrifuged to separate serum from the blood samples. The separated serum was reacted on a microplate coated with capture Ab (antibodies), IL-1β antibody or IL-18 antibody. IL-1β antibody or IL-18 antibody, which is a capture Ab (antibodies), is reacted with an antibody bound to a reactive substrate, and the absorbance is measured using a microplate reader to detect IL-1β and IL-18, which are inflammatory cytokines in the serum. The level was measured.

As shown in Figure 5, the levels of IL-1β and IL-18 were found to be significantly increased in the serum of AOSD-induced IFN-γ knockout mice (IFN KO CFA) and normal mice (Wild). On the other hand, in mice administered TIP-1 or MIP-2 peptide at a concentration of 10 nmol/g, the levels of IL-1β and IL-18, which were increased by AOSD induction, were significantly reduced.

[Example 4] Histological analysis of animal tissue

Lymph node and spleen tissue of the mouse in which AOSD was induced in Example 2 was dehydrated and washed to make a paraffin block, and the tissue in the paraffin block was cut at 4 μm and hematoxylin and eosin (H&E, hematoxylin) Cytoplasmic and cell nuclear staining with (and eosin) was performed to evaluate inflammatory cell infiltration.

As shown in Figure 6, the lymph nodes and spleen of AOSD-induced mice (CFA) showed enlarged cells and increased cell numbers, and infiltration of inflammatory cells was observed in spleen cells. However, mice treated with TIP-1 or MIP-2 at a concentration of 10 nmol/g (CFA+TIP1 or CFA+MIP2) showed a decrease in inflammatory cell formation similar to the normal control group (PBS). Therefore, it was confirmed that the concentration of inflammatory cells in the tissue was improved through TIP-1 or MIP-2.

The description of the present invention described above is for illustrative purposes, and those skilled in the art will understand that the present invention can be easily modified into other specific forms without changing the technical idea or essential features of the present invention. will be. Therefore, the embodiments described above should be understood in all respects as illustrative and not restrictive.

The scope of the present invention is indicated by the claims described below, and all changes or modified forms derived from the meaning and scope of the claims and their equivalent concepts should be construed as being included in the scope of the present invention.

Claims (16)

TIP-1 (TLR inhibitor peptide 1) or MIP-2 (MAL/MyD88 inhibitory peptide 2) peptide; Or a polynucleotide encoding the peptide; A pharmaceutical composition for treating or preventing autoinflammatory diseases comprising as an active ingredient. The pharmaceutical composition according to claim 1, wherein the TIP-1 (TLR inhibitor peptide 1) is a peptide consisting of the amino acid sequence represented by SEQ ID NO: 1. The pharmaceutical composition according to claim 1, wherein the MIP-2 (MAL/MyD88 inhibitory peptide 2) is a peptide consisting of the amino acid sequence represented by SEQ ID NO: 2. The pharmaceutical composition according to claim 1, wherein the autoinflammatory disease is Still's disease or adult-onset Still's disease (AOSD). The pharmaceutical composition according to claim 1, wherein the pharmaceutical composition inhibits the activity of IL-1β or IL-18. The pharmaceutical composition according to claim 1, wherein the pharmaceutical composition inhibits enlargement of the spleen or lymph nodes. TIP-1 (TLR inhibitor peptide 1) or MIP-2 (MAL/MyD88 inhibitory peptide 2) peptide; Or a polynucleotide encoding the peptide; A pharmaceutical composition for preventing or treating enlargement of the spleen or lymph nodes, comprising as an active ingredient. The pharmaceutical composition according to claim 7, wherein the pharmaceutical composition inhibits enlargement of the spleen or lymph nodes caused by Still's disease or adult-onset Still's disease (AOSD). TIP-1 (TLR inhibitor peptide 1) or MIP-2 (MAL/MyD88 inhibitory peptide 2) peptide; Or a polynucleotide encoding the peptide; A health functional food composition for improving or preventing auto-inflammatory diseases containing as an active ingredient. TIP-1 (TLR inhibitor peptide 1) or MIP-2 (MAL/MyD88 inhibitory peptide 2) peptide; Or a polynucleotide encoding the peptide; A health functional food composition for improving or preventing enlargement of the spleen or lymph nodes, comprising as an active ingredient. A method of preventing or treating an autoinflammatory disease comprising administering TIP-1 (TLR inhibitor peptide 1) or MIP-2 (MAL/MyD88 inhibitory peptide 2) to a subject in a therapeutically effective amount. A method for preventing or treating enlargement of the spleen or lymph nodes, comprising administering TIP-1 (TLR inhibitor peptide 1) or MIP-2 (MAL/MyD88 inhibitory peptide 2) to a subject in a therapeutically effective amount. Use of TIP-1 (TLR inhibitor peptide 1) or MIP-2 (MAL/MyD88 inhibitory peptide 2) for the prevention or treatment of autoinflammatory diseases. Use of TIP-1 (TLR inhibitor peptide 1) or MIP-2 (MAL/MyD88 inhibitory peptide 2) for the prevention or treatment of spleen or lymph node enlargement. Use of TIP-1 (TLR inhibitor peptide 1) or MIP-2 (MAL/MyD88 inhibitory peptide 2) for the manufacture of drugs for the prevention or treatment of autoinflammatory diseases. Use of TIP-1 (TLR inhibitor peptide 1) or MIP-2 (MAL/MyD88 inhibitory peptide 2) for the manufacture of drugs for the prevention or treatment of spleen or lymph node enlargement.

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