Route-dependent immunomodulation: local stimulation by a surfactant and systemic stimulation by a polyanion.

Immunomodulatory activity of the two synthetic adjuvants dimethyldioctadecylammonium bromide (DDA) and dextran sulfate (DXS) in relation to route and time of injection was investigated in mice. Humoral responses to sheep red blood cells (SRBC) were measured as the number of direct anti-SRBC plaque-forming cells (PFC) in the spleen 5 days after immunization. Both adjuvants stimulated the anti-SRBC response if adjuvant and antigen were injected simultaneously via the same route (either intraperitoneally or intravenously). Administration of adjuvant and antigen via different routes (intraperitoneally or intravenously, respectively or vice versa) resulted in enhanced humoral responses after DXS, but not after DDA. Intraperitoneal immunization of mice which were injected intraperitoneally with either adjuvant 4 days earlier resulted in diminished humoral responses. Immune responses in pretreated mice were not suppressed when the antigen was injected intravenously instead of intraperitoneally. In conclusion, DDA and DXS differ in immunostimulating properties as DDA enhanced only a response to antigen injected via the same route whereas DXS induced a systemic state of increased immunoresponsiveness. The immunosuppressive state induced by intraperitoneal injection of either adjuvant prior to immunization is restricted to the peritoneal compartment. Mechanisms underlying differences between both adjuvants and aspects of systemic immunopotentiation are discussed.