Inflammation and Related Phenomena 125 



remains of other tissue cells in addition) . It is probably formed by 

 the action of proteases liberated from the dead leucocytes on the 

 proteins of these and other cells. 



The process of repair whereby acutely inflamed tissues are re- 

 stored to normal or converted to an avascular scar is complex. Poly- 

 morphs are replaced by macrophages, lymphocytes and sometimes 

 plasma cells, fibroblasts migrate into the region and lay down re- 

 ticulum and collagen and new blood vessels, lymphatics and nerves 

 also grow into the damaged area. It seems very likely that these 

 events are controlled by locally released or activated endogenous 

 substances. Unfortunately almost nothing is known of these hypo- 

 thetical local hormones. The cortisone group of drugs is very effec- 

 tive in inhibiting the process of repair and it may be that their 

 action will one day provide a clue as to the nature of the controlling 

 mechanism. 



The actual process of collagen formation is thought to begin as 

 the elaboration of mucopolysaccharide ground substance by fibro- 

 blasts and macrophages and possibly by vascular endothelium. This 

 then appears to be followed by secretion of a protein termed pro- 

 collagen from macrophages and fibroblasts. Pro-collagen has a mole- 

 cule of globular configuration which is converted to the fibrillar 

 molecule of collagen possibly by interaction with ground substance. 

 In vitamin C deficiency, in which wound healing is notoriously 

 slow, ground substance is formed normally but the later stages fail 

 to develop. Cortisone on the other hand acts at an earlier stage by 

 inhibiting migration and proliferation of fibroblasts. It has been 

 suggested that this is in fact secondary to similar inhibition of new 

 blood vessel formation and migration. 



PAIN 



Some of the pain felt in inflamed tissues is undoubtedly due to 

 direct stimulation of sensory nerve endings. The accumulation of 

 fluid exudate in a confined tissue space would itself cause such 

 stimulation and lead to prolonged pain. On the other hand, many 

 endogenous substances released or activated by injury cause pain 

 on injection or application to a raw surface such as a blister base. 

 Thus histamine is moderately active in this respect, as is acetyl 



