Intercellular immunological controls and modulation of cyclic AMP levels. Some doubts

We have re-examined two sets of observations put forward to support the hypothesis that rises in cAMP levels induced by vasoactive amines and prostaglandins are involved in the intercellular control of immunological and inflammatory processes. (1) This hypothesis is said to be supported by the fact that cholera toxin, which raises cAMP levels in lymphoid tissue in vivo, is immunosuppressive. However, we found that cholera toxin inhibited antibody production only if given in doses causing gross destruction of lymphoid tissue. This sort of evidence, therefore, cannot be used to support a hypothesis about homoeostasis under physiological conditions. (2) The hypothesis is also said to be supported by the claim that vasoactive amines, prostaglandins, cholera toxin and methyl xanthines, which raise cAMP levels in cells in vitro, also inhibit the formation of haemolytic plaques by spleen cells from mice immunized with sheep red cells. However, we were unable to confirm this claim, except when the experimental conditions were such that cells were killed or other artefacts operated.