126 The Chemistry of the Injured Cell 



choline. 5-H.T. is a much more powerful pain-producer and so are 

 a variety of peptides of the kinin type. The globulins themselves do 

 not cause striking pain on injection nor, as far as is known, do the 

 substances that cause leucocyte emigration. In another category the 

 nucleoside xanthosine and its base xanthine cause intense pain on 

 injection in very small amounts (Moulton et al., 1954) . Thus there 

 are many suitable endogenous substances whose liberation might 

 account for pain in inflammation. It is not yet possible to say which 

 are the more important at any particular stage in the inflammatory 

 cycle. However, it is known that release of 5-H.T. occurs very soon 

 after injury. In addition, bradykinin, a pain-producing peptide, is 

 formed in plasma within a minute or two of the fluid making con- 

 tact with glass. These tw_Q endogenous compounds are therefore at 

 the moment the most likely candidates for the role of chemical 

 mediator of pain in inflammation (Armstrong et al., 1957) . 



FEVER 



It might be thought that fever which is so much a feature of 

 infections of all kinds is a direct result of the invading organisms on 

 the body. However, pyrexia occurs also in disease not associated 

 with invasion by microorganisms, particularly if there has been 

 destruction of tissue, e.g. in burns or infarction (death of tissue due 

 to sudden loss of blood supply as in the heart in coronary throm- 

 bosis) . 



It has been known since 1884, that pus will cause fever if in- 

 jected into animals. This effect was later attributed to bacterial 

 products when it was discovered that endotoxin, i.e. extracts of dead 

 bacteria, especially gram-negative bacilli, also caused pyrexia on 

 injection. These endotoxins are polysaccharides or lipopolysac- 

 charides and being relatively heat-stable are apt to contaminate 

 even sterilised solutions and apparatus, constituting the so-called 

 pyrogens. Similar pyrogenic polysaccharides are present in many 

 animal and plant tissues (Bennett and Cluff, 1957) . 



When endotoxin or similar polysaccharides are injected, the 

 resultant fever is characteristic. There is a latent period before the 

 body temperature begins to rise and in addition the number of 

 circulating white cells falls (leucopenia) followed by a rise (leuco- 



