In Vivo Suppression by Cholera Toxin of Cell-Mediated and Foreign Body Inflammatory Responses

Abstract

Cholera toxin (CT) injected i.v. into mice resulted in a rise in cyclic AMP levels in splenic white cells. This was associated with and followed by a marked and relatively prolonged decrease in both the spleen cells and circulating lymphocytes. The effect of CT on a series of cell-mediated immunologic reactions related to the pathogenesis of schistosomiasis was then tested. CT profoundly suppressed dermal footpad swelling to soluble schistosome egg antigens, granuloma formation around schistosome eggs injected into the pulmonary microvasculature of unsensitized and sensitized mice, production of macrophage migration inhibition factor by intact granulomas (obtained from the livers of infected mice) maintained in vitro in tissue culture, and it ameliorated portal hypertension and esophageal varices in hepatosplenic schistosomiasis. In addition CT significantly prolonged allograft survival in mice even though it was first administered 6 days after grafting. Finally, CT completely eliminated foreign body granuloma formation around plastic beads (used as controls for the egg granulomas) which is a nonimmunologic reaction due to activation of chemical mediators of inflammation.