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Induction of interleukin 1 by synthetic and naturally occurring muramyl peptides
Abstract:
Like bacterial lipopolysaccharides (endotoxins), synthetic muramyl peptides (MPs) are thought to exert many of their biological effects by inducing the production of various mediators from host cells. Both synthetic muramyl dipeptide (MDP) and naturally occurring sleep factor (SF), which contains an MP structure, stimulate human monocytes to produce interleukin 1 (IL 1). IL 1 is a family of unique polypeptides that mediate a variety of host defense functions and possess several biological properties, many of which are shared with MPs. Endotoxins are potent inducers of IL 1, but polymyxin B, which blocks endotoxin's biological activities, has no effect on MP-induced IL 1 production. SF purified from human urine and SF isolated from the peritoneal fluid of patients undergoing chronic ambulatory peritoneal dialysis (CAPD) induce IL 1 when incubated with human mononuclear cells in vitro. SF from urine or CAPD fluid induces IL 1 production in the picrogram per milliliter range whereas synthetic MDP requires microgram per milliliter concentrations. Thus, both synthetic and naturally occurring MPs exert their biological effects, in part, by inducing IL 1.
Insights
Synthetic and natural muramyl peptides (MPs) stimulate interleukin 1 (IL 1) production in human monocytes. This immune mediator plays a key role in host defense, similar to endotoxins but via a distinct mechanism.
Area of Science:
- Immunology
- Molecular Biology
- Biochemistry
Background:
- Bacterial lipopolysaccharides (endotoxins) and synthetic muramyl peptides (MPs) are known to induce host cell mediators.
- Interleukin 1 (IL 1) is a key mediator in host defense with properties overlapping those of MPs.
- Polymyxin B blocks endotoxin activity but not MP-induced IL 1 production, suggesting different pathways.
Purpose of the Study:
- To investigate the role of muramyl peptides (MPs) in stimulating interleukin 1 (IL 1) production.
- To compare the IL 1-inducing capacity of synthetic and naturally occurring MPs.
- To elucidate the mechanism of MP-induced IL 1 production in human monocytes.
Main Methods:
- Incubation of human monocytes with synthetic muramyl dipeptide (MDP) and naturally occurring sleep factor (SF).
- Measurement of interleukin 1 (IL 1) production.
- Comparison of effective concentrations for synthetic MDP versus SF.
Main Results:
- Both synthetic muramyl dipeptide (MDP) and naturally occurring sleep factor (SF) stimulate human monocytes to produce interleukin 1 (IL 1).
- Naturally occurring SF, purified from urine or peritoneal dialysis fluid, is a more potent inducer of IL 1 than synthetic MDP.
- SF induces IL 1 at picogram per milliliter concentrations, while synthetic MDP requires microgram per milliliter concentrations.
Conclusions:
- Synthetic and naturally occurring muramyl peptides (MPs) exert biological effects, in part, by inducing interleukin 1 (IL 1) production.
- Naturally occurring MPs are significantly more potent inducers of IL 1 than their synthetic counterparts.
- The findings highlight IL 1 as a common mediator for both synthetic and natural MPs.