T-cell-dependent immunobiological activity of a desmuramyl analog of muramyl dipeptide, adamantylamide dipeptide (AdDP), and D-isoglutamine

Immune-related edemagenic activity of glutamines and glutamic acid, components of immunomodulatory agents

“…This effect has proved to depend on activation of a Tcell/macrophage cooperation and I>isoglutamine has been suggested as a functional determinant for this action [10]. The present findings which show that similar proinflammatory potential is possessed by other D-isoglutamine-containing peptides may be regarded as a solid piece of evidence to support this view.…”

“…Our previous results demonstrated that synthetic immunomodulatory agent of bacterial origin, MDP, as well as its desmuramyl analog AdDP can rapidly induce an exudative type of transient inflammation in mice [9,10]. This effect has proved to depend on activation of a Tcell/macrophage cooperation and I>isoglutamine has been suggested as a functional determinant for this action [10].…”

“…It seems highly improbable to suppose that the reducing effects of these agents are mediated by counterirritation as they themselves are unable to produce any edema (see Table 2). We have suggested earlier [9,10] that inflammation produced by AdDP or MDP is probably initiated by augmented production of some immunoregulatory/inflammatory cytokines like IL-1, TNF, MIP-1, etc. The suppressive effects of dexamethasone, a well-recognized inhibitor of their production [13][14][15], might indicate that some of these factors could be involved also in formation of edema induced by other derivatives of AdDP, as well as by glutamine and glutamic acid.…”

“…They were prepared and administered as described earlier [9,10]. Briefly, fresh solutions in apyrogenic water (1 : 10 dilution) were given i.p.…”

“…Our recent findings confirmed this assumption for a desmuramyl analog of MDP, adamantylamide-L-alanyl-i>isoglutamine (AdDP). Both agents possess overlapping biological activities [5][6][7][8] including the enhancing influence on generalized vascular permeability [9,10]. This effect was shown to depend on activation of T-cell/macrophage interaction(s) leading finally to enhanced biosynthesis of proinflammatory eicosanoids, a putative consequence of augmented production of certain immunoregulatory/inflammatory cytokines [9,10].…”