ABSTRACT
The anti-complementary effects of the surface-active immunological adjuvants dimethyldioctadecylammonium bromide (DDA) and pluronic polyols L101 and L121 were investigated in the mouse system. All three adjuvants showed complement (C)-inactivating effects. DDA caused a time- and dose-dependent reduction of alternative pathway (AP) and overall C activity, which varied with the serum concentration. Polyols induced a preferential inactivation of the AP by a more direct mechanism. A rather general, causative relationship between anti-complementary and immunological adjuvant activities is suggested. This might involve interference with nonspecific elimination of antigen, counteraction of immunosuppression by terminal C components, and/or moderation of C3b-mediated reduction of Ia-expression, leading to a better antigen presentation.
Subject(s)
Adjuvants, Immunologic/pharmacology , Complement Activation/drug effects , Surface-Active Agents/pharmacology , Animals , Complement Pathway, Alternative/drug effects , DDT/analogs & derivatives , DDT/immunology , DDT/pharmacology , Dose-Response Relationship, Drug , Female , Male , Mice , Mice, Inbred Strains , Poloxalene/pharmacology , Rabbits , Time FactorsABSTRACT
Complement (C) inactivation by ammonia, ethylenediamine and methylamine in mouse serum was studied in relation to a possible adjuvant effect of the substances in a cell-mediated immune response. The amines caused a dose-dependent depletion of both alternative pathway (AP) and overall C activity in vitro and showed also pronounced adjuvant effects in the delayed type hypersensitivity response of mice to SRBC. A significant correlation between momentary inhibition of AP activity and adjuvanticity was observed (r = 0.9995; P approximately 0.02), suggesting a causative relationship between these two phenomena. Both effects seem to be a direct function of the number of amino-groups per molecule. Since, on the other hand, lysosomotropic activity of amines is known to decrease with the number of amino-residues, our findings exclude an important role of direct phagocyte inhibition in the immuno-adjuvanticity of these compounds. A longer persistence and improved presentation of antigen as indirect result of local C-depletion could account for the immunological adjuvant effects of amines.
