CYTOXPACE

ROLE OF INTERLEUKIN-2

Interleukin-2 (IL-2) is a cytokine primarily involved in the regulation of the immune system, playing a central role not only in immune responses but also in pathological processes such as systemic inflammation, genotoxicity, and cellular senescence.

An excess of IL-2 may contribute to the development of autoimmune diseases, including rheumatoid arthritis, systemic lupus erythematosus, and thyroiditis. Conversely, reduced levels may suggest a compromised immune response, as seen in immunodeficiencies. The evaluation of IL-2 is therefore useful in distinguishing between autoimmune conditions and chronic infections. Moreover, severe systemic inflammation associated with elevated IL-2 levels may cause damage to the cardiovascular system, leading to hypotension, arrhythmias, or ischaemia.

IL-2-induced activation of T cells can generate reactive oxygen species (ROS), resulting in DNA damage and increased vulnerability to genotoxic stress. This phenomenon, which is exacerbated in contexts of chronic inflammation, can lead to errors in DNA replication and incomplete repair, thereby promoting genomic instability. The action of IL-2 on the immune system, mediated through uncontrolled cell proliferation and oxidative stress, underscores its significance in the mechanisms underlying genomic damage and alterations in DNA repair.

AGING PROCESSES

Stem cell damage and the accumulation of DNA lesions accelerate aging, compromising the repair and regeneration capacity of tissues. This process leads to a rapid decline in organic functions and increases the risk of age-related diseases.

ROLE OF INTERLEUKIN-4

Monitoring Interleukin-4 (IL-4) levels is crucial for assessing the state of the immune system, particularly in the context of allergic, inflammatory, autoimmune, infectious, and oncological conditions. This cytokine plays a key role in the development of allergic diseases such as asthma, rhinitis, and atopic dermatitis, as well as in anaphylaxis and systemic lupus erythematosus. In addition, it contributes to chronic inflammation.

IL-4 shapes the inflammatory environment by promoting the production of reactive oxygen species (ROS) and other toxic molecules that damage DNA. Furthermore, it interferes with DNA repair mechanisms, impairing the body’s ability to correct damage and increasing the risk of mutations. IL-4 also provides survival signals to cells with compromised DNA, hindering their programmed cell death (apoptosis) and encouraging the proliferation of mutated cells, with a potential risk of malignant transformation.

AGEING PROCESSES

As stem cell function and availability decline, tissues lose the ability to effectively repair damage or sustain cellular renewal. This accelerates ageing processes and increases susceptibility to age-related diseases.

Genomic instability, promoted by a chronically inflamed environment and elevated levels of genotoxic stress, leads to mutations that hasten the functional decline of tissues and contribute to the onset of age-associated conditions.

In summary, although IL-4 plays a vital role in immunity and inflammatory response, altered levels indirectly contribute to genotoxicity, genomic instability, and stem cell depletion, thereby accelerating the ageing process.

ROLE OF INTERLEUKIN-6

Interleukin-6 (IL-6) plays a significant role in various immune, inflammatory, and stress response processes. It is produced in response to infections, trauma, or immune stimuli, and acts both as a promoter of inflammation and a regulator of immune responses. IL-6 contributes to tumour progression, genotoxicity, and genomic instability by modulating the cellular microenvironment and DNA repair mechanisms, thereby supporting the survival of genetically damaged cells and increasing the risk of mutations during cell proliferation.

Elevated levels of IL-6 have been associated with:

• Rheumatoid arthritis: contributing to joint damage and systemic inflammation
• Systemic lupus erythematosus
• Multiple sclerosis: promoting neuroimmune inflammation
• Endothelial inflammation: fostering atherosclerosis and cardiovascular diseases

In addition to its pro-inflammatory action, IL-6 plays a central role in chronic and systemic inflammation. For this reason, it is considered both a diagnostic marker and a therapeutic target in a wide range of conditions.

AGEING PROCESSES

High IL-6 levels contribute to increased genotoxicity and genomic instability, compromising the vitality and function of stem cells and accelerating ageing processes through the promotion of chronic inflammation and cellular senescence.

ROLE OF INTERLEUKIN-10

Monitoring Interleukin-10 (IL-10) levels is essential for assessing the balance between inflammation and immunosuppression. Elevated levels may indicate the body’s attempt to counteract excessive acute inflammation or systemic inflammation. Conversely, low levels may reflect inadequate resolution of inflammation, which increases the risk of chronicity and tissue damage.

Abnormal IL-10 levels are particularly indicative of autoimmune conditions, such as:

• Rheumatoid arthritis: reduced IL-10 levels may be associated with increased joint inflammation
• Systemic lupus erythematosus: IL-10 levels may be elevated as a compensatory mechanism to reduce inflammation
• Multiple sclerosis: low levels may exacerbate neuroinflammation

Interleukin-10 plays a crucial role in maintaining intestinal mucosal homeostasis, and altered levels are associated with diseases such as Crohn’s disease and ulcerative colitis.

In the context of Genotoxicity and Genomic Instability, IL-10 plays a dual role:

• Protective: it reduces DNA damage caused by chronic inflammation and oxidative stress
• Permissive: it may support the survival of damaged cells and contribute to tumour progression through immunosuppression

AGEING PROCESSES

A deficiency of IL-10 may promote chronic inflammatory states, accelerating the ageing process and impairing organ function. Although its anti-inflammatory effects generally offer protection against genotoxicity and genomic instability, altered or insufficient IL-10 levels may indirectly contribute to these issues by increasing inflammation. This results in reduced stem cell vitality and an acceleration of ageing processes.

ROLE OF INTERLEUKIN-12

Monitoring Interleukin-12 (IL-12) levels is essential for evaluating and modulating the immune response across a wide range of conditions, from chronic infections and tumours to autoimmune diseases and persistent inflammation. IL-12 is a crucial cytokine involved in regulating both innate and adaptive immunity, providing valuable information about the body’s capacity to respond to intracellular pathogens, tumours, and inflammation-based disorders. IL-12 exerts both direct and indirect effects on genotoxicity and genomic instability. It stimulates the production of reactive oxygen species (ROS), which cause oxidative stress and DNA damage, thereby contributing to genotoxicity. IL-12 plays a key role particularly in diseases such as Crohn’s disease and psoriasis.

AGEING PROCESSES

The inflammatory environment caused by high levels of IL-12 promotes tissue ageing both directly (through cellular damage) and indirectly (by reducing the number of available stem cells). This acceleration of tissue senescence leads to the decline of organ function and increases vulnerability to chronic age-related diseases.

Inadequate regulation of IL-12 impairs immune system functionality, contributing to the deterioration of immune responses and accelerating cellular and tissue ageing.

Thus, IL-12, by influencing immune responses and promoting inflammation, is associated with elevated levels of genotoxicity and genomic instability—factors which reduce stem cell functionality and accelerate the ageing process.

ROLE OF INTERLEUKIN-17A

IL-17A plays a central role in many inflammatory and autoimmune diseases, such as psoriasis and psoriatic arthritis, rheumatoid arthritis, multiple sclerosis, systemic lupus erythematosus, Crohn’s disease, and ulcerative colitis, as well as in infectious diseases. It contributes to the activation of prolonged inflammatory responses and amplifies immune activity. By stimulating the release of cytokines that induce oxidative stress and damage DNA, IL-17A promotes chronic inflammation and thereby indirectly supports genotoxicity and genomic instability.

Moreover, IL-17A increases the risk of genomic instability by altering the cellular microenvironment, disrupting DNA repair mechanisms, and promoting genetic mutations.

In addition to its involvement in the pathogenesis of numerous inflammatory and autoimmune diseases, IL-17A also contributes to endothelial dysfunction and the progression of atherosclerotic plaques. Elevated levels are associated with vascular inflammation and atherosclerosis.

STEM CELL CONCENTRATION AND AGEING PROCESSES

An inflammatory environment sustained by high levels of IL-17A is particularly harmful to stem cells, as it induces cellular senescence and reduces the regenerative capacity of tissues and organs. Inflammation leads to a reduction in the stem cell population and impairs their regenerative function.

This decline in stem cell number and activity contributes to the progressive deterioration of tissue structure and function, a hallmark of ageing and a condition strongly associated with an increased risk of chronic age-related diseases.

ROLE OF INTERFERON-GAMMA

Interferon-gamma (IFN-γ) is a cytokine with both pro-inflammatory and regulatory functions, essential for the immune system. It plays a crucial role in regulating immune responses, inflammation, and defence against infections and tumours. However, its action is also associated with genotoxicity and genomic instability, as it can contribute to DNA damage and disruption of genomic integrity, particularly through chronic inflammation, oxidative stress, and the cellular response to injury.

IFN-γ is vital in combating intracellular infections of bacterial, viral, and parasitic origin due to its ability to activate macrophages, enhance the activity of antigen-presenting cells (APCs), and stimulate immune responses. Nonetheless, its persistent release may contribute to chronic inflammation, as seen in Crohn’s disease and ulcerative colitis, maintaining a pathological state. In autoimmune diseases—such as rheumatoid arthritis, multiple sclerosis, and type 1 diabetes—it amplifies immune activation and exacerbates tissue damage.

IFN-γ fosters a pro-mutagenic microenvironment via chronic inflammation, impairs DNA repair mechanisms, and promotes genomic instability, especially in tumour contexts. Although it may increase the expression of pro-apoptotic molecules to eliminate cells with DNA damage, this mechanism may become ineffective in the presence of chronic inflammation or cancer, allowing genetically unstable cells to survive.

The main mechanisms through which IFN-γ contributes to genotoxicity and genomic instability include:

• Induction of ROS and RNS, causing direct DNA damage
• Support of a pro-mutagenic environment through chronic inflammation
• Disruption of DNA repair mechanisms, increasing the risk of mutations
• Modulation of the tumour microenvironment, favouring the accumulation of genomic instability

ACCELERATION OF AGEING PROCESSES

Extended exposure to IFN-γ accelerates stem cell senescence and ageing of other tissue cells, contributing to the accumulation of dysfunctional cells, decline in tissue function, and hence to tissue senescence. Its effects may be deleterious, promoting genotoxicity, reducing stem cell vitality, and hastening the ageing process. Monitoring and modulating IFN-γ levels is essential to prevent complications related to genetic damage in inflammatory, autoimmune, and oncological conditions.

TUMOUR NECROSIS FACTOR-α (TNF-α)

Monitoring Tumour Necrosis Factor-α (TNF-α) levels is essential to understand and manage many pathophysiological conditions, particularly those related to chronic inflammation and autoimmunity.

TNF-α is a pro-inflammatory cytokine widely used as a biomarker for diagnosing and monitoring the progression of disease. In acute conditions—such as trauma, infections, and burns—TNF-α is rapidly released to initiate the inflammatory response and is therefore essential for immune system activation.

However, in chronic conditions—such as rheumatoid arthritis, psoriasis, and inflammatory bowel diseases—persistently elevated levels of TNF-α contribute to disease pathogenesis and progression, making it a diagnostic and therapeutic target. Its role in chronic inflammation, increased oxidative stress, and modulation of the cellular and tumour microenvironment links TNF-α closely to genotoxicity and genomic instability.

This makes TNF-α a central player in the connection between chronic inflammation, genetic damage, and complex diseases such as cancer and degenerative disorders.

STEM CELL CONCENTRATION AND AGEING PROCESSES

Inflammation and excessive production of TNF-α can alter the microenvironment that supports stem cells, reducing their capacity for self-renewal and inducing senescence or cell death. TNF-α decreases the regenerative effectiveness required to repair tissues and organs, thus contributing to the acceleration of ageing.

In particular, the following effects are observed:

• Contribution to Cellular Senescence: Chronic exposure to TNF-α can promote cellular senescence, a process in which cells cease to divide and secrete various cytokines and inflammatory mediators, further exacerbating local inflammation and tissue damage.

• Deterioration of Tissue Function: Accumulation of DNA damage, loss of functional stem cells, and increased cellular senescence reduce the tissue’s ability to repair itself and accelerate functional decline—key phenomena in the ageing process.

ROLE OF HIGH-SENSITIVITY C-REACTIVE PROTEIN (HS-CRP)

High-sensitivity C-reactive protein (hs-CRP) is a key biomarker for assessing the inflammatory status of the body. It is produced primarily by the liver in response to inflammatory stimuli mediated by cytokines such as IL-6 and TNF-α. In clinical practice, hs-CRP is used to diagnose, monitor, and manage both inflammatory and chronic conditions, as well as to estimate cardiovascular risk. However, its significance extends beyond inflammation monitoring, as it is closely associated with genotoxicity and genomic instability, particularly in the context of chronic inflammation.

hs-CRP reflects the intensity of systemic and subclinical inflammation. Elevated or persistently high hs-CRP levels are observed in:

• Autoimmune diseases, such as rheumatoid arthritis, systemic lupus erythematosus, and vasculitis
• Inflammatory bowel diseases, including Crohn’s disease and ulcerative colitis
• Chronic metabolic conditions, such as obesity, type 2 diabetes mellitus, and metabolic syndrome

Moreover, moderately elevated hs-CRP levels are predictive of cardiovascular risk, as they indicate vascular wall inflammation, which plays a role in the progression of atherosclerosis, myocardial infarction, and stroke.

Although indirectly, hs-CRP plays a significant role in genotoxic and genome-destabilising processes through the following mechanisms:

• Chronic inflammation: persistent inflammatory states promote a pro-mutagenic microenvironment characterised by oxidative stress and the release of reactive oxygen species (ROS) and reactive nitrogen species (RNS), which cause DNA damage

• Modulation of the cellular microenvironment: chronic inflammation alters DNA repair mechanisms, increasing the risk of somatic mutations. This effect is particularly evident in tissues exposed to chronic inflammation, such as the colon (e.g., ulcerative colitis) and the liver (e.g., non-alcoholic steatohepatitis)