Immunotherapy Mechanism of Azithromycin

Azithromycin is a macrolide antibiotic with a long half-life. It can bind to the 50S ribosome subunit of bacteria to prevent protein synthesis and effectively inhibit bacterial growth. Therefore, it is one of the first-choice specific drugs for clinical anti-infectious treatment. In recent years, studies have found that azithromycin can improve and treat a variety of diseases by regulating the body's immune system. For example, azithromycin can affect the activities of neutrophils, macrophages, and T cells, improving the body's ability to resist various pathogens; by regulating these immune cells, it can also help the body regulate inflammation such as TNF-α and IL-10 in the body. The level of cytokines can effectively slow down the inflammatory response and improve inflammatory tissue damage. In addition, azithromycin has been used in the research of immune deficiencies and autoimmune diseases due to its powerful immunomodulatory ability and has achieved some breakthrough results. Its immunotherapy potential has attracted widespread attention in the immunological community. Clinical application of azithromycin combination therapy has achieved remarkable results. The number of effective cases is also gradually increasing. This article reviews the research on the immunotherapy mechanism of azithromycin.

Figure 1. Inflammatory response signaling pathway.(Parnham MJ, et al.; 2014)

Regulation of Neutrophils by Azithromycin

Neutrophils have strong inflammatory chemotaxis and can kill pathogens through strategies such as degranulation, phagocytosis, production of reactive oxygen species, and extracellular trapping and sterilizing nets (NETs). The regulatory effect of azithromycin on neutrophils has been confirmed in the treatment of inflammatory bowel disease (IBD). Researchers used a dextran sulfate sodium (DSS)-induced mouse colitis model to evaluate the therapeutic effect of azithromycin on IBD. The results showed that the neutrophil chemotactic factor (NCF) in the colon tissue of mice in the azithromycin + DSS group was lower than that in the DSS group, granulocyte colony-stimulating factor (G-CSF) and pro-inflammatory cytokine TNF-α levels were significantly reduced, the migration and aggregation of neutrophils at the inflammatory site was reduced, and inflammatory symptoms were significantly improved. NETs are an important means for neutrophils to kill pathogens. When the body is stimulated by pathogens, NETs can be released extracellularly to form a physical barrier to hinder the spread of pathogens and increase the concentration of local antibacterial factors. However, the release of NETs can also cause One of the causes of autoimmune disease. Other researchers have found that azithromycin can significantly reduce the release of NETs, degranulation and ROS production of neutrophils stimulated by phorbol 12-myristate 13-acetate (PMA) under in vitro conditions, and has a negative impact on activated neutrophils. The cells have a stabilizing effect and thereby alleviate autoimmune symptoms caused by the release of NETs.

Figure 2. Effects of azithromycin (AZM) on the immune system. (Parnham MJ, et al.; 2014)

Azithromycin Modulates Acquired Immunity

Acquired immunity is the specific immunity produced by the body against pathogens. T cells are the main members of the acquired immune system and play a pivotal role in cellular immunity and humoral immunity. Research on the effect of azithromycin on the acquired immune system is currently focused on Its regulation of T cell activity.

Diffuse panbronchiolitis (DPB) is a fatal lung disease caused by inflammation of respiratory bronchioles that spreads to pulmonary bronchioles. The increased number and overactivation of T cells in the bronchus of patients with DPB leads to the excessive secretion of a variety of chemokines such as MIP-1α, CXCL-2 and the inflammatory cytokine IL-17A, causing immune disorders and promoting the occurrence of DPB. Azithromycin can promote the formation of T cell autophagosomes by inhibiting the phosphorylation of the downstream target protein S6 ribosomal protein (S6RP) in the mTOR pathway. It can also significantly inhibit the proliferation of patients' T cells and promote apoptosis. It reduces the levels of IL-17A and CXCL-2 in patients with DPB, prevents the accumulation of inflammatory cells, relieves inflammation, and has a good therapeutic effect on DPB.

Application of Azithromycin in Autoimmune Diseases

Autoimmune diseases refer to a series of diseases caused by the immune system becoming immune to self-antigens and attacking its own tissue cells under the influence of various factors. There are many causes of autoimmune diseases, and there is a lack of universal and effective therapeutic drugs. Azithromycin has shown important application value in autoimmune diseases due to its immunomodulatory effect.

Psoriasis is one of the most common autoimmune diseases. It has a long course and is easy to relapse or even persist throughout life. However, the pathogenesis of psoriasis is still unclear. Experiments have shown that azithromycin can attenuate imiquimod-induced lysosomal acidification in dendritic cells and the maturation of Toll-like receptors 7 (TLR-7) in lysosomes, block TLR-7 signaling on DCs, and reduce the production of key cytokines such as IL-17a, IL-17f, IL-22 and IL-23 in the pathogenesis of psoriasis, effectively improving the symptoms of patients and becoming a potential drug for the treatment of psoriasis.

Another important research result comes from the treatment of systemic lupus erythematosus (SLE). SLE is a multi-system autoimmune disease with a high incidence rate, and the actual treatment process often treats the symptoms rather than the root cause. Compared with healthy people, patients with SLE have lower macrophage phagocytic activity and an imbalance in the ratio of M1/M2 macrophages. Excess M1 macrophages cause persistent inflammatory responses. Through a series of in vivo and in vitro experiments, the researchers confirmed that azithromycin can promote the phosphorylation of protein kinase B, target the PI3K/Akt signaling pathway, promote the polarization of macrophages toward the M2 type, and stabilize the dynamic balance of different subtypes of macrophages in the body. It can effectively relieve SLE.

Azithromycin Related Antibodies

Azithromycin Related Antigen

Azithromycin Related ELISA