The physiological mechanisms by which various hypersensitivity phenomena manifest themselves are poorly understood. Presumably, the various types of hypersensitivity reactions result from either a systemic or localized release of pharmacological agents. The specific pharmacologic agents involved in allergic or hypersensitivity reactions are known with some cer-tainty for only a few animal species. Histamine is of great importance in anaphylaxis of the guinea pig and rabbit, and serotonin has been implicated in the mouse and in the rat. Other pharmacological agents have also been implicated in hypersensitivity reactions, such as the" slow reacting substance," bradykinin, acetylcholine, and others less well known. Histamine, by far, has been best studied. It is a potent, naturally occurring amine known to produce vasodilatation, promote capillary permeability, and induce bronchoconstriction. Marked differences in susceptibility to histamine exist among animal species. Guinea pigs and rabbits are highly susceptible to the lethal effect of histamine, whereas mice and rats have a remarkable tolerance to it (Table 1). It has been known for several years that the toler-ance of at least some strains of rats and mice can be greatly diminished by administering certain bacterial substances. An understanding of how these substances sensitize animals to histamine would increase our knowledge of hypersensitivity in general. This review attempts to summarize the present knowledge of bacterial substances which have been reported to enhance sensitivity of animals to histamine.

Most of the observations in this field have been made with cells from smooth cultures of Bor-detella pertussis or with extracts therefrom. The literature dealing with other microorganisms consists mainly of isolated observations on histamine sensitization produced in animals. Little or no work has been reported on the mode of action and the purification of the sensitizing substances from microorganisms other thanB. pertussis. This re-view covers various aspects of the histamine sensitization phenomenon, and discusses the relation-ship of this sensitization to other phenomena associated with thetreatment of animals with histamine-sensitizing materials. The nature of the substances producing sensitization and the vari-ous postulated mechanisms of action of these intriguing substances will be also discussed. Reviews have appeared which cover various aspects of this topic (71, 100, 107, 152, 154, 205, 217, 223). The present review will emphasize recent advances and topics not well covered previously.