NATURE 



[September 2, 1915 



Further, it appears that a weaker solution of iodoform 

 (i : 500,000) yields a still higher phagocytosis (61-4 per 

 C5ent.). The explanation of this phenomenon will after- 

 wards be given. It is seen that in still weaker concen- 

 trations the phagocytosis is diminished, but even in a 

 solution of I- iodoform to 5,000,000 salt solution, the 

 promoting effect of iodoform is still perceptible, for 

 it is 47-1 per cent., whereas in a pure NaCl solution it 

 was ^(44 + 437) =43-9 per cent. 



The favouring effect of iodoform is still more 

 evident when the leucocytes are placed for several 

 hours in a pure NaCl solution. Then the phago- 

 cytosis falls to a considerable extent. Sometimes the 

 phagocytes are quite paralysed. The addition of iodo- 

 form in a concentration i : 5,000,000 then raises the 

 phagocytic power by 30 per cent, or more. Thus there 

 is no doubt that iodoform is able to promote phago- 

 cytosis. 7^ it the iodine or the iodoform as such? 

 We have found that iodine is noxious in a high degree. 

 We must conclude, therefore, that iodoform as such 

 causes the increase of the phagocytic power. 



The question now suggests itself : How can the 

 favourable effect of iodoform be explained? It may be 

 accepted from numerous investigations that the outer 

 layer of the cells consists of a fatty substance, a so- 

 called lipoid membrane. Now iodoform is soluble in 

 fat, and it is quite obvious that such a membrane 

 will grow more soft and more flexible after having 

 absorbed iodoform, and that consequently the plas- 

 ticity and mobility will be facilitated. 



If this interpretation be correct, then other sub- 

 stances soluble in fat, such as chloroform, chloral, 

 alcohol, benzine, camphor, fatty acids (propionic, 

 butyric acids) should affect phagocytosis in a similar 

 way. This is found to be invariably the case. 



(3) Effect of Chloroform, Alcohol, Camphor, Benzine, 

 and other Substances Soluble in Fat on Phagocytosis. 

 I shall not give an account of all our experiments 

 made in this direction. I only give as an example an 

 experiment with chloroform, from which one can at 

 once get an idea as to the exactitude of the method. 

 It was soon found that dilutions i : 2000, i : 6000, and 

 also I : 10,000 paralysed the phagocytes. The follow- 

 ing table contains some experiments with weaker 

 solutions : — 



Effect of Chloroform on Phagocytosis. 



Percentage of leucocytes 

 F'U'a* havine taken ud carbon 



having uken up cart 

 Per cent. 



NaCl 0'9 per cent. 



Chloroform i : 20,000 .. 



I : 100,000... 



I : 500,000. 



I : 5,000,000 



ri?|xxoo=40-6 



•• 1^x100=41.2 

 1 562 



f^ HI* X 100=50-8 



480 



-5x100 = 49-8 

 .451 



^xioo = 6o-6| 

 l'.t 60-3 



40-9 



50-3 



100 = 60-1 



:455 



.r _ 



ii?xioo=S9-i'^ 



370 



379, 



868 



208 M4'3 



■J 



ioo=43-6| 

 100=45 J 



From this table it appears that chloroform 

 I : 20,000 raises the phagocytosis power from 40-9 

 per cent, to 50-3 per cent. ; further, that phagocytosis 

 NO. 2392, VOL, 96] 



is considerably increased by chloroform i : 100,000, in 

 which case it rises to 60-5 per cent. Evidently in the 

 chloroform-solution i : 20,000 the paralysing influence 

 also makes itself felt. In a dilution of i : 500,000 the 

 favourable effect remains to about the same extent 

 as in I : 100,000, and finally in a solution of i chloro- 

 form to 5,000,000 NaCl-solution, this favourable effect 

 is still visible, though slight. 



Similar results were obtained with benzine, camphor, 

 turpentine, alcohol, chloral, fatty acids (propionic and 

 butyric), and also Peruvian balsam. These all, without 

 exception, promoted phagocytosis. Hence our hypo- 

 thesis for explaining the effect of iodoform was fully 

 confirmed. Another strong support to our hypothesis 

 was obtained by comparing the concentrations of the 

 named substances which were able to increase phago- 

 cytosis. It appeared that the relation between these 

 concentrations corresponded with that existing between 

 the solubility of these substances in fat. 



Further, all the substances applied in very small 

 doses showed a stimulating effect, but paralysed when 

 given in greater quantities. This can be explained by 

 distinguishing two factors. First, slight quantities of 

 the substance by dissolving in the outer layer of the 

 cell weaken it and increase the plasticity and mobility. 

 Then, greater quantities having entered the cell, a 

 second factor, the paralysing effect on the protoplasm, 

 comes into play. As the amount of chloroform is 

 increased, the paralysing effect gets the precedence 

 and no carbon at all is taken up. 



4. Other Phenomena seen in the Light of the 

 ■Foregoing Facts. 



The effect of fat-dissolving substances on phagocytes 

 throws a new light on several facts which were until 

 now for the most part entirely unexplained. In the 

 first place, we may refer to the power of turpentine 

 to cause local exudations, and the favourable effect of 

 a subcutaneous injection of the same substance in the 

 treatment of pneumonia with horses and of mastitis 

 with cows, which for some time has been practised 

 with great success in France, Denmark, and Holland. 

 Experiments made by us in this direction have shown 

 that there is much reason to attribute this effect to 

 very small quantities of turpentine dissolving in the 

 lymph of tissue-spaces and afterwards entering the 

 blood circulation and promoting the phagocytic power 

 of the phagocytes in lung and udder. 



In the same way we can explain the marked effect 

 of camphor-treatment in inflammatory processes of 

 the uterus and its adnexa, an effect not understood 

 hitherto. Then there is the great effect of covering 

 infected wounds with "balsam of Peru," the thera- 

 peutic value of inhalation of turpentine-vapour in 

 tuberculous and other infectious processes in the 

 respiratory organs. 



In all these cases a stimulating action on the phago- 

 cytes, and probably also on other cells (granulation- 

 cells), which play a part in the healing process, may 

 come into play. Yet more becomes clear to us from 

 the above researches. 



It is well known that various narcotics applied in 

 smaller doses have a stimulating effect and paralyse in 

 greater quantities. Engelmann observed this many 

 years ago on ciliated cells, but he did not try to 

 explain it. Also as regards the nervous system we 

 know with regard to chloroform and ether that, when 

 administered, they first cause excitement and after- 

 wards insensibility. So far as we know, this contrast 

 has never been explained, but when viewed in connec- 

 tion with our experiments, the phenomenon becomes 

 clear. In the beginning of narcosis only small quan- 

 tities have entered into the nerve cells. The conse- 

 quence is a softening in the first place of the outer 

 layer. This weakened state of the cells produces an 



