Inflammation and Related Phenomena 111 



mine plays its part early in the inflammatory reaction and that 

 other mechanisms may then come into operation. 



This hypothesis was confirmed with the aid of anti-inflamma- 

 tory drugs (Spector, 1958) . When animals in which pleurisy has 

 been induced with turpentine are pre-treated with small doses of 

 an anti-histamine drug, the appearance of the exudate is delayed 

 for one or two hours. After this delay the exudate develops nor- 

 mally, even if repeated doses of the anti-histaminic are admin- 

 istered. The effect of anti-histamines could also be achieved by 

 prior depletion of bodily histamine. A precisely similar result is 

 obtained in numerous species when inflammation is induced by a 

 standard thermal injury (Spector and Willoughby, 1959; Wilhelm, 

 1959) . Here the passage of plasma from the vessels into the 

 damaged tissues is again delayed by prior dosage with a specific 

 anti-histamine drug. Again, too, repeated doses fail to prevent the 

 subsequent appearance of the inflammatory cycle. 



These results show that the role of histamine in inflammation 

 is to initiate the vascular changes, especially increased capillary 

 permeability, and that the subsequent sustenance of these changes 

 is due to other mechanisms independent of histamine release. The 

 rapidity with which the effects of histamine occur after injury may 

 be explained by assuming that the amine is released from mast 

 cells, which adjoin blood vessels in large numbers and which are 

 rich in histamine. These cells are known to be disrupted and 

 liberate their granules in response to injury. The precise mechan- 

 ism of histamine release by injury is unknown. Uvnas (1958) has 

 suggested that the membrane of mast cells contains an enzyme 

 capable of lysing the membrane and thus releasing the cellular 

 content of histamine and that injury activates this enzyme. Other 

 workers have suggested that injury leads to the formation of sur- 

 face-active compounds, e.g. peptides which have a similar effect on 

 the mast cell membrane. Apart from these ideas, the release of 

 histamine has been postulated to follow rupture of a peptide or 

 polar bond linking histamine to a protein, or an ion-exchange re- 

 action releasing histamine from loose combination with an acidic 

 body compound. Mast cells contain a trypsin-like enzyme and 



