Summary
Muramyl dipeptide or MDP (AcMur-L-Ala-D-iGln) is a synthetic immunoadjuvant which can also enhance non-specific resistance to bacterial infections in mice, even by the oral route. By the use of several derivatives, it has been shown that neither adjuvanticity nor pyrogenicity was a perequisite for eliciting an increased resistance, and that unwanted pharmacological effects can be eliminated by minor chemical modifications. Moreover, some lipophilic analogs or derivatives obtained by linking the glycopeptide to a carrier were found to be more active than MDP. Their effectiveness also depended on the dose and the timing of administration, and varied according to the bacterial challenge. The most appropriately timed administration of MDP and derivatives was established between one and four days before the challenge. In some cases, MDP was protective even when injected one hour after the challenge, whereas with other immunostimulants such as lipopolysaccharides or BCG, a negative phase of higher susceptibility may occur under these conditions. MDP still enhanced resistance to bacterial infections in animals with a poor immune status, like newborns or adult mice under immunosuppressive treatment. Moreover, the protective activity was not impaired after repeated injections of large doses of MDP or other adjuvant analogs, a treatment which is known to inhibit specific immune responses.
Zusammenfassung
Muramyl-Dipeptid oder MDP (AcMur-L-Ala-D-iGln) ist ein synthetisches Immunadjuvans, das sogar bei oraler Verabreichung die unspezifische Abwehr gegen bakterielle Infektionen bei Mäusen verstärken kann. Durch Anwendung verschiedener Derivate wurde belegt, daß weder Adjuvans-Aktivität noch Pyrogenität die Voraussetzung für eine Steigerung der Abwehr sind und daß unerwünschte pharmakologische Wirkungen durch geringfügige chemische Modifikationen ausgeschaltet werden können. Es fand sich außerdem, daß einige lipophile Analoga oder Derivate, die durch Bindung des Glykolipids an einen Carrier gewonnen wurden, aktiver sind als MDP. Ihre Wirksamkeit war ebenfalls dosisabhängig und wurde vom Zeitpunkt der Applikation beeinflußt; sie variierte außerdem entsprechend der Größe der bakteriellen Belastung. Als günstigster Applikationszeitraum für MDP und seine Derivate hatte sich Tag eins bis vier vor dem Setzen der Infektion erwiesen. In manchen Fällen wirkte MDP sogar protektiv, wenn es eine Stunde nach Infektion injiziert wurde, während unter dieser Voraussetzung mit anderen Immunstimulantien wie LPS oder BCG eine negative Phase mit erhöhter Anfälligkeit auftreten kann. Bei Tieren mit schwacher Abwehrlage wie neugeborenen Mäusen oder erwachsenen Tieren nach immunsuppressiver Behandlung wurde die Resistenz gegen bakterielle Infektionen durch MDP noch erhöht. Nach wiederholter Injektion von MDP oder Analoga mit Adjuvans-Aktivität in hohen Dosen (die bekanntlich spezifische Immunreaktionen hemmen) wurde außerdem die protektive Wirkung nicht beeinträchtigt.
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Parant, M., Chedid, L. Stimulation of non-specific resistance to infections by synthetic immunoregulatory agents. Infection 13 (Suppl 2), S251–S255 (1985). https://doi.org/10.1007/BF01644439
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DOI: https://doi.org/10.1007/BF01644439