Cytokines

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Background

What are Cytokines?

Cytokines are small protein molecules that act as intercellular messengers. They are produced by immune cells and play an important role in the immune system's communication and response. Cytokines are involved in regulating cellular processes in response to various stimuli, including microbial infections, injuries, and tumors. They are responsible for the activation, proliferation, differentiation, and migration of immune cells, and they also exert immunomodulatory effects by influencing the behavior and function of other cells.

What are the structure of cytokines?

Cytokine Structure

Cytokines are small proteins, with a molecular weight between 8,000 and 70,000 Da. They are characterized by their three-dimensional structure, which is mostly composed of alpha-helices and beta-sheets. Cytokines can be either soluble or membrane-bound, with different configurations based on their specific functions. They have hydrophobic and hydrophilic regions, allowing them to interact with the extracellular matrix and bind to receptors on the surface of target cells.

Function of Cytokines

The primary function of cytokines is to regulate cellular processes in response to various stimuli. They are involved in the immune response to infections, inflammations, and tumors. Cytokines are essential for the activation and differentiation of immune cells, including T and B lymphocytes, natural killer cells, and macrophages. They also play a role in hematopoiesis, the formation of blood cells from stem cells.

Cytokines have different functions depending on the context in which they are produced. Some cytokines, such as interleukin-1 (IL-1) and tumor necrosis factor-alpha (TNF-alpha), are pro-inflammatory cytokines that trigger inflammation by inducing the production of other cytokines and chemokines. Other cytokines, such as interleukin-10 (IL-10) and transforming growth factor-beta (TGF-beta), are anti-inflammatory cytokines that suppress the immune response and promote tissue repair.

Applications

Medical Treatment: Cytokines are used in medicine to boost the immune response in patients with conditions like cancer, HIV, and hepatitis. They can also decrease immune responses in disorders like rheumatoid arthritis or Crohn's disease.

Anti-inflammatory Agents: Some cytokines, like interleukin-10, are used as anti-inflammatory agents in conditions like psoriasis or inflammatory bowel disease.

Vaccine Development: Cytokines are also used in vaccine development. They can help to enhance the body's immune response to the vaccine.

Regulating Cell Growth: Some cytokines act as growth factors, regulating cell growth and proliferation. They may be used in treating conditions involving abnormal cell growth, such as cancer.

Treatment of Wound and Injuries: Certain cytokines play an essential role in wound healing and tissue repair and thus can be used in the treatment of wounds and injuries.

Bone Growth: Some cytokines, like bone morphogenic proteins, are used in promoting bone growth and repair.

Diagnosis and Monitoring: Levels of certain cytokines in the blood can help identify specific diseases or monitor disease progression.

Cell differentiating agents: Certain cytokines help to induce differentiation of stem cells into specific cell types. This can be useful in regenerative medicine and the treatment of various diseases.

Fertility treatment: In reproductive medicine, cytokines play a role in processes such as ovulation, fertilization, and embryo implantation.

Research: Cytokines are important tools in biomedical research, particularly in studying the immune system and developing new treatments for diseases.

Case Study

Case 1: Ou W, Zhao Y, Wei A, et al. Serum cytokine pattern in children with hemophagocytic lymphohistiocytosis. Ann Hematol. 2023 Apr;102(4):729-739. doi: 10.1007/s00277-023-05132-6. Epub 2023 Feb 16. PMID: 36792730; PMCID: PMC9931565.

This study aimed to compare the serum levels of 34 cytokines of children with hemophagocytic lymphohistiocytosis (HLH) and explored the specific cytokine pattern of HLH subtypes and the relationship between cytokine levels and prognosis. Various cytokines play important roles in HLH. Different subtypes of HLH have their specific cytokines pattern, and the ratio of cytokines may be more significant in differentiating HLH subtypes than the single one. Elevated GM-CSF and MCP-1 could be useful biomarkers for a poor prognosis for patients with HLH.

Fig1. Different levels of IL-6, IL-10, Eotaxin, IL-13, IFN-γ, MIP-1β, and IL-18 in HLH subtypes

Fig1. Different levels of IL-6, IL-10, Eotaxin, IL-13, IFN-γ, MIP-1β, and IL-18 in HLH subtypes

Case 2 : VanDyke D, Iglesias M, Tomala J, et al. Engineered human cytokine/antibody fusion proteins expand regulatory T cells and confer autoimmune disease protection. Cell Rep. 2022 Oct 18;41(3):111478. doi: 10.1016/j.celrep.2022.111478. PMID: 36261022; PMCID: PMC9631798.

Low-dose human interleukin-2 (hIL-2) treatment is used clinically to treat autoimmune disorders due to the cytokine's preferential expansion of immunosuppressive regulatory T cells (Tregs). However, off-target immune cell activation and short serum half-life limit the clinical potential of IL-2 treatment. Recent work showed that complexes comprising hIL-2 and the anti-hIL-2 antibody F5111 overcome these limitations by preferentially stimulating Tregs over immune effector cells. Results of this article provide a roadmap for IC design and establish a Treg-biased immunotherapy that could be clinically translated for autoimmune disease treatment.

Fig1. F5111 IC blocks IL-2 binding to IL-2Rβ and biases toward Treg activation (A) Equilibrium biolayer
        interferometry-based titrations of F5111 antibody (Ab), hIL-2, control IC, hIL-2/F5111 complex (Cx, 1:1 molar
        ratio), and F5111 IC LN35 binding to hIL-2 (left), hIL-2Rα (middle), or hIL-2Rβ (right).

Fig1. F5111 IC blocks IL-2 binding to IL-2Rβ and biases toward Treg activation (A) Equilibrium biolayer interferometry-based titrations of F5111 antibody (Ab), hIL-2, control IC, hIL-2/F5111 complex (Cx, 1:1 molar ratio), and F5111 IC LN35 binding to hIL-2 (left), hIL-2Rα (middle), or hIL-2Rβ (right).

Case 3: Abe N, Kono M, Kono M, et al. Cytokine and chemokine multiplex analysis-based exploration for potential treatment and prognostic prediction in large-vessel vasculitis: A preliminary observational study. Front Immunol. 2022 Nov 23;13:1066916. doi: 10.3389/fimmu.2022.1066916. PMID: 36505494; PMCID: PMC9727250.

Large-vessel vasculitis (LVV) is subclassified into two phenotypes; Takayasu arteritis and giant cell arteritis. Although the pathogenesis of LVV is not fully established, IL-6-IL-17 axis and IL-12-IFN-γ axis play critical roles in the disease development. This article aimed to clarify the association between the disease state and cytokine/chemokine levels, to assess disease course as prognosis and to predict regulators in patients with LVV using the blood profiles of multiple cytokines/chemokines.

Fig1. Multiplex blood cytokine/chemokine analysis results in the untreated and treated patients with large-vessel
        vasculitis (LVV).

Fig1. Multiplex blood cytokine/chemokine analysis results in the untreated and treated patients with large-vessel vasculitis (LVV). Twenty-one blood samples from 21 patients with LVV in active or inactive state were examined using multiplex cytokines/chemokines analysis. A dot plot with a line shows individual cases.

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