Cold Atmospheric Plasma in the Treatment of Autoimmune Diseases: Mechanisms, Applications, and Prospects

Abstract

Background: Autoimmune diseases, including rheumatoid arthritis (RA), are characterized by an aberrant immune responses that leads to chronic inflammation and tissue damage. Traditional treatments, such as immunosuppressive drugs, only provide symptomatic relief and often cause significant side effects. Cold atmospheric plasma (CAP), a form of nonthermal plasma, has emerged as a potential therapeutic tool, offering antimicrobial, anti-inflammatory, and immune-modulatory effects.

Objective: This review aims to explore the mechanisms of CAP, its application in autoimmune diseases, and its potential to improve existing treatments.

Methods: The review synthesizes recent studies investigating the biological effects of CAP, particularly its interaction with immune cells. Key mechanisms discussed include the generation of reactive oxygen and nitrogen species (ROS/RNS), which modulate immune responses, promote wound healing, and target pathogenic cells. The therapeutic potential of CAP in treating autoimmune diseases, such as RA, atopic dermatitis, allergic contact dermatitis, psoriasis, and vitiligo is examined through current research findings.

Results: Studies have demonstrated that CAP can modulate fibroblast-like synoviocytes in RA, reducing their viability and inducing apoptosis. In skin diseases like atopic dermatitis, CAP has been shown to alleviate symptoms and reduce microbial load by altering the skin microbiome. In psoriasis, CAP suppresses Th17 cell differentiation and reduces keratinocyte hyperproliferation. Additionally, CAP enhances wound healing by promoting macrophage M2 polarization and collagen remodeling. Despite promising results, concerns remain about the long-term safety of CAP, particularly regarding the accumulation of ROS/RNS.

Conclusion: CAP offers a novel approach for treating autoimmune diseases by modulating immune responses, enhancing drug efficacy, and promoting tissue repair. Its ability to selectively target pathogenic cells and its antimicrobial properties make it a promising therapeutic tool in autoimmune diseases.

Keywords: autoimmune disease; cold atmospheric plasma; inflammation; treatment.

Figure 1

States of matter: Solid, liquid, gas, and plasma. This diagram illustrates the four fundamental states of matter: solid, liquid, gas, and plasma. Plasma is characterized by a mixture of ions, electrons, ultraviolet (UV), reactive oxygen species (ROS) and reactive nitrogen species (RNS).

Figure 2

The immunoregulatory and therapeutic mechanisms of cold atmospheric plasma (CAP) in immune‐related diseases. CAP generates a variety of ions, electrons, ultraviolet (UV), reactive oxygen species (ROS) and reactive nitrogen species (RNS), which together modulate the local tissue environment and cellular behavior. In rheumatoid arthritis (RA), CAP induces apoptosis in RA fibroblast‐like synoviocytes (RA‐FLS), promotes G2/M cell cycle arrest, and inhibits migration and invasion. In atopic dermatitis (AD) and allergic contact dermatitis (ACD), CAP reduces skin inflammation by suppressing mast cell infiltration, lowering cytokine levels (e.g., IL‐9, TSLP, TNF‐α), and rebalancing skin microbiota. In psoriasis, CAP inhibits Th17 cell differentiation, reduces keratinocyte hyperproliferation, and alleviates skin lesions. In vitiligo, CAP downregulates IFN‐γ and CXCL10 expression, limits CD3⁺ and CD8⁺ T cell infiltration, and enhances NRF2‐mediated antioxidant defense, promoting melanocyte survival and repigmentation. In chronic wounds, CAP enhances macrophage M2 polarization, improves macrophage metabolic activity (OXPHOS, FAO), promotes collagen remodeling, and accelerates tissue repair. This figure was created by the authors using adapted elements from Servier Medical Art (https://smart.servier.com/), licensed under CC BY 4.0 (https://creativecommons.org/licenses/by/4.0/).

Figure 3

Prospects of cold atmospheric plasma (CAP) therapy for autoimmune diseases. This diagram illustrates five potential directions for applying CAP in the treatment of autoimmune diseases: (1) Enhance the biocompatibility of implants—improving tissue integration and reducing the risk of implant loosening. (2) Prevent microbial infections after joint replacement—leveraging CAP's antimicrobial properties to reduce biofilm formation. (3) Enhance drug efficacy—increasing immune cell sensitivity to conventional therapies. (4) Impact on Immune Cells—adjusting cytokine profiles and cell surface markers to reduce inflammation. (5) Selectivity Inhibit Pathogenic Cells—inducing apoptosis in hyperactive or autoreactive immune cells while sparing normal tissue. This figure was created by the authors using adapted elements from Servier Medical Art (https://smart.servier.com/), licensed under CC BY 4.0 (https://creativecommons.org/licenses/by/4.0/).