In VivoStudies on the Influence of Bacteriophage Preparations on the Autoimmune Inflammatory Process

Abstract

Phage preparations used for phage therapy may have not only direct antibacterial action but also immunomodulating effects mediated by phages themselves as well as by bacterial antigens. Therefore phage application in patients with immune disorders, and especially with autoimmune diseases, requires special attention. The aim of this study was to investigate the effect of phage lysates (staphylococcal phages A3/R, phi200, and MS-1 cocktail, enterococcal phage 15/P, Pseudomonas phage 119x, and E. coli T4 phage) as well as purified T4 phage on the course of murine collagen-induced arthritis (CIA), commonly used as an animal model of rheumatoid arthritis. Intraperitoneal application of phage lysates or purified T4 phage did not aggravate the course of autoimmune joint disease. Moreover, although endotoxins are known to potentiate CIA, the systemic administration of phage lysate of Pseudomonas aeruginosa, which contains debris of this Gram-negative bacillus, did not significantly influence CIA although the sonicate of the corresponding bacterial strain did. Interestingly, a purified T4 phage revealed some anti-inflammatory activity when applied under the therapeutic scheme. Our preliminary results do not suggest that phages may aggravate the symptoms of rheumatoid arthritis. In contrast T4 phage may even exert an immunosuppressive effect.

Therapeutic potential of phages in autoimmune liver diseases

“…Deletion of KC in experimentally induced hepatitis suppresses liver damage as well as collagen-induced autoimmune arthritis in mice [31]. Interestingly, we noted similar effects of phages using the latter model of autoimmune disorder [12]. KC may also be involved in mediating the phenomenon of liver allograft tolerance, which occurs in different species so that transplant survival may be accomplished without concurrent immunosuppression -a long-term dream in transplantation [32].…”

“…Recently, another support for our concept was provided by the data showing that in a mouse model of autoimmune disorder phages can inhibit the development of autoimmune inflammatory responses with efficacy comparable to standard immunosuppression [12].…”

“…In brief, phages can diminish T cell activation, alloantigeninduced immunoglobulin production in vitro and extend the skin allograft survival in naive and sensitized mice [13,14]. In addition, phages may reduce autoimmune reaction when a mouse model of autoimmunity was used (collagen-induced arthritis) [12]. Skin and organ inflammatory infiltration induced by alloantigens and endotoxin can also be reduced markedly by phage or a phage protein administration [13,20].…”

“…In the face of increasing drama of anti-microbial resistance, phages offer a broad medical promise as a weapon against antibiotics-resistant bacteria [10]. However, phages should no longer be considered as mere bacterial viruses but also as potential modulators of immunity [11][12][13][14][15][16], a finding which may have an important application in therapy including autoimmune diseases [12].…”

Phage therapy in allergic disorders?

“…TLR4# (10) Leukocytosis# (31) Degranulation of granulocytes - (12) Autoimmune reaction # (13) Inflammatory infiltration of skin (32) and lung (33) # Local reactions to phage administered subcutaneously - (34) Note: Relevant references are given in parentheses. # downregulation, " upregulation, -no effect.…”