While bacteriophages were previously viewed simply as "bacteria killers," it is now known that they play a vital role in the immune system of mammals, much like commensal microflora. Specifically, phage therapy exhibits a powerful anti-inflammatory effect (reduced levels of C-reactive protein and other inflammatory markers) even when bacteria are not destroyed, suggesting that the therapeutic effect of bacteriophages is not limited to antibacterial activity.

Phages have been shown to stimulate the production of the proinflammatory interleukin-1 (IL-1) receptor antagonist and significantly increase the synthesis of interleukin-10. Interleukin-10 is a cytokine with potent anti-inflammatory activity that blocks the expression of proinflammatory cytokines and inhibits the activity of Th1 T-helper cells, natural killer cells, and macrophages. Phages have also been shown to prevent granulocyte degranulation in humans and significantly reduce inflammation caused by autoimmune reactions.

Evidence has accumulated that IL-10, a cytokine elevated by phages, is a potent inhibitor of allergic inflammation and airway hyperresponsiveness. Administration of IL-10 reduces the number of eosinophils and mast cells, which reduces nasal mucosal inflammation and, therefore, has the potential to alleviate allergic rhinitis.

There is also evidence that allergic disorders such as asthma, rhinitis, and atopic dermatitis may be mediated by oxidative stress. Endogenous and exogenous reactive oxygen species (ROS), as demonstrated in animal models, are responsible for inflammation and airway hyperresponsiveness in asthma. Therefore, it is important to note that phages, unlike pathogenic viruses and bacteria, do not induce the formation of ROS and inhibit their production in phagocytes.

Lung and gut microbiomes have recently been shown to be involved in the pathogenesis of asthma and allergies. Children with allergic diseases have elevated levels of E. coli and Staphylococcus aureus. It is also known that local allergic reactions can be caused by microorganisms. Because phages, unlike antibiotics, typically have a narrow specificity, they can be used to eliminate bacterial pathogens that trigger allergic reactions.

Thus, bacteriophages exhibit anti-inflammatory effects in vitro and in vivo and can attenuate abnormal immune responses. Observations of patients receiving phage therapy show that allergic reactions to the phages themselves are rare. However, the antiallergic properties of phages appear promising and require further research.

* Andrzej Gorski, Ewa Jonczyk-Matysiak, Marzanna Łusiak-Szelachowska, Ryszard Miedzybrodzki, Beata Weber-Dabrowska and Jan Borysowski. Phage therapy in allergic disorders? Experimental Biology and Medicine, 2018, 243: 534-537 . DOI: 10.1177/1535370218755658