128 The Chemistry of the Injured Cell 



centre than if given into a peripheral vein. Endotoxin caused an 

 equally delayed pyrexia given by both routes. 



However, later work showed that the initial phase of fever fol- 

 lowing injection of endotoxin is probably due to a direct action of 

 the endotoxin and that it is only after some hours have elapsed that 

 fever can be said to be wholly due to endogenous pyrogen. Further- 

 more, it has also been demonstrated that an endogenous pyrogen 

 indistinguishable from that of leucocyte extracts is present in sterile 

 exudates even in the virtual absence of leucocytes brought about by 

 administration of nitrogen mustard (Bennett and Beeson, 1953). 

 Little is known of the chemical nature of endogenous pyrogen. It is 

 a non-diffusible and therefore large molecule and relatively heat- 

 labile. A likely guess would be that it is a glycoprotein or mucopro- 

 tein. 



It seems, therefore, that at least four pyrogenic compounds may 

 be operative in injury and inflammation; polysaccharides derived 

 from microorganisms or from damaged tissues and endogenous 

 pyrogen derived from polymorph leucocytes and at least one other 

 source. Many tissues have been studied but so far only polymorph 

 leucocytes have yielded an extract with the properties of endo- 

 genous pyrogen (Wood, 1958) . 



LEUCOCYTOSIS 



No aspect of the phenomena associated with inflammation has 

 proved more intractable than leucocytosis. This is due partly to the 

 complexity of the response itself. Thus in inflammation due to 

 pyogenic microorganisms or certain viruses, e.g. poliomyelitis and 

 rabies, or associated with sterile but extensive destruction of tissue, 

 there is an increase in the level of circulating polymorph leucocytes. 

 However, other infections, bacterial and viral are associated with a 

 drop in the number of circulating polymorphs. In this category are 

 typhoid fever, brucellosis, influenza and measles. Moreover, in 

 other virus diseases, notably glandular fever and pertussis, there is 

 an increase in the level of circulating lymphocytes. In other condi- 

 tions, usually of an allergic or parasitic origin there is an increase in 

 the number of circulating eosinophil leucocytes. 



The situation is complicated further by the fact that, unlike 



