Induction of various cytokines in mice and activation of the complement system in rats as a part of the mechanism of action of the Corynebacterium granulosum-derived P40 immunomodulator

Abstract

The capacity of the Corynebacterium granulosum‐derived P40 immunomodulator to induce in mice the formation of various cytokines IFN, IL‐1, IL‐2, α‐TNF as well as to activate the complement system in rats was investigated. The results showed that P40 injected by the intravenous route was capable of inducing the formation of all four cytokines. High levels of IFN were measured 2 h after P40 stimulation and were still present at 24 h. The kinetic study of IL‐1, IL‐2 and α‐TNF induction showed that it was a biphasic phenomenon. The patterns of IL‐1 and α‐TNF induction were quite comparable, whereas the release of IL‐2 was delayed with respect to that of IL‐1 and α‐TNF. Oral administration of P40 to rats strongly activated the alternative pathway of the complement system. It was concluded that most of the non‐specific effects of P40 on the immune system are likely to be mediated by its capacity to induce cytokine formation and to activate the complement system.

The PorB porin from commensal Neisseria lactamica induces Th1 and Th2 immune responses to ovalbumin in mice and is a potential immune adjuvant

“…Examples of adjuvants are oil emulsions [4][5][6], squalene (MF59) [7], immune stimulating complexes (ISCOMs [8,9]) with Quil-A and both gram-negative bacteria and bacterial products [4,[10][11][12]. These include DNA with immunostimulatory CpG motifs (one of the most powerful adjuvants [13]), Bordetella pertussis toxin [2,14], Corynebacterium granulosum derived P40 component [15], MPL [16], Mycobacterium and its components (Freund adjuvant) [4,17], Cholera toxin [18] and porins from various organisms such as Fusobacterium nucleatum [19], Shigella [20][21][22], Salmonella [22,23] and Neisseria meningitidis and gonorrhoeae [24][25][26][27][28][29].…”

Evaluation of hyaluronic acid-P40 conjugated cream in a mouse model of dermatitis induced by oxazolone

“…P40 is a particulate fraction or fragment isolated from Corynebacterium granulosum (now called Propionibacterium acnes ), that was first described in 1970 by a group of researchers at the Pasteur Institute in Paris, and has previously been studied for its pleiotropic effect ( 1 ). P40 has been demonstrated to perform a wide spectrum of pharmacological functions including, antitumor effects via a marked inhibitory activity towards ‘liquid’ and solid tumors in mice ( 2 ), adjuvant effects ( 3 ), immunomodulatory effects ( 4 ), effects on phagocytosis ( 5 , 6 ), antimicrobial properties on bacterial infections ( 7 ), effects on viral infections ( 8 ), cytokine induction ( 9 ) and effects on Escherichia coli infections ( 10 ). In animal models, it has been demonstrated that P40 exhibits dichotomous action in immune-mediated diseases by increasing the production of antibodies against sheep red blood cells and augmenting the resistance of mice towards bacterial infections ( 4 ).…”