Influence of indomethacin on various immunopharmacological effects of muramyl dipeptide (MDP).

Muramyl dipeptide (MDP) is a low molecular (less than 500 daltons) synthetic analogue of a streptococcal peptidoglycan subunit. It was demonstrated to be the minimal structure essential for eliciting the adjuvant effect ascribed to Freund's complete adjuvant (FCA). MDP was likewise shown to represent the minimal requirement for peptidoglycan-induced changes in temperature and it was at first concluded that there was an almost perfect correlation between pyrogenicity and adjuvant activity. However, other experiments showed that certain MDP derivatives were as adjuvant active without eliciting a febrile response in the rabbit. Moreover an anti-inflammatory substance such as indomethacin completely inhibits the pyrogenic effect of MDP but does not affect or even enhance various of its immunostimulant properties. Inhibition of MDP-induced fever is not associated with modification of leucopenia or production of circulating endogenous pyrogens observed after MDP injection. Indomethacin incubated with peritoneal macrophage cultures at a dose which blocks prostaglandin synthesis, does not decrease the production by MDP of endogenous pyrogens.