ENDOTOXIN IMPEDES VASOCONSTRICTION IN THE SPLEEN - ROLE OF ENDOGENOUSINTERLEUKIN-1 AND SYMPATHETIC INNERVATION

Processes relevant for an appropriate immune response such as immune c ell traffic and recirculation require a tight control of blood supply to lymphoid organs. Interactions between endogenous cytokines and symp athetic nerve fibers in lymphoid organs can contribute to this control . The results reported in this paper show that 1) administration of lo w doses of lipopolysaccharide (LPS), an endotoxin derived from gram-ne gative bacteria, causes an increase in splenic blood flow (SBF); 2) th is increase is mediated by the production of endogenous interleukin-1 (IL-1); 3) the effect of LPS on SBF requires an intact splenic sympath etic innervation; 4) the LPS-induced increase in SBF is exerted at the postganglionic level; 5) the endotoxin inhibits the vasoconstriction induced by the in vivo stimulation of the splenic nerve but does not a ffect the vasoconstriction induced by norepinephrine (NE); and 6) alth ough IL-1 and LPS stimulate general sympathetic activity as reflected by increased peripheral vascular resistance, they do not increase NE c oncentration in splenic dialysates. Together these in vivo results ind icate that endogenous IL-1 affects blood supply to the spleen by inhib iting the sympathetic vasoconstrictor tonus at a postganglionic, preju nctional level. This effect is expected to be relevant for immune cell recirculation, homing, and traffic as well as antigen trapping in the spleen, an organ specialized in the control of these processes during immune responses.