The study of the defense of the organism against fatty acids focusses attention once again on the adrenals whose constituents appear to be part of the natural defense mechanism. To date, around 30 different crystalliz able compounds have been isolated from less than a third of the total cortical extract. The amorphous part, biologically more active than the crystallized part, would contain other important compounds. Even if some of them are intermediary compounds or artefacts, adrenal intervention still is characterized by plurality of its active agents. Furthermore, several opposite tendencies are recognized between groups of adrenal compounds. While all the corticoids show a certain antagonistic action toward fatty acids, mineralocorticoids are, from several points of view, antagonistic to neoglucogenics.

With these considerations in mind, and recognizing the adrenals as one of the principal means for relatively rapid defense against noxious agents, we have investigated the relationship of the adrenals to lipids.

We have already noted the striking richness of the adrenals in arachidonic acid. About 25% of the total fatty acid content of the glands is made up of this acid which is found only in small quantities in other organs. We also found pentaenes and hexaenes present in greater amounts than in other organs. These fatty acids must have a biological purpose and two hypotheses can be advanced. According to one mentioned previously, (Note 11, Chapter VI), the corticoids would be synthesized from arachidonic acid through cyclization. According to the second hypothesis, arachidonic acid, as well as other high fatty acids present in the adrenals, would be used as active functional fatty acids. Secreted by the adrenals, they would pass into the circulation and intervene as needed by the organism, especially for immediate defense purposes.

We have seen that an intervention of polyunsaturated fatty acids occurs in the first defense response of an organism to a noxious agent. These acids are responsible for the exaggerated oxidation processes through which the organism attacks the noxious agents themselves or the heterogenized constituents resulting from their action. We consider that some of the fatty acids intervening in this defense mechanism are liberated locally, especially if they appear in response to a condition limited to a lower entity. In this case, they would come from changes induced in the constituents of the entity itself. The local intervention of lipolytic enzymes would lead to a liberation of free fatty acids. In a defense response for the organism as the highest entity, the actively intervening fatty acids appear in the general circulation in the first phase of the diphasic phenomenon. Some of these fatty acids would be of adrenal origin, liberated at these moments. In the second phase of the defense mechanism, a further liberation of steroids by the adrenals would occur, aimed at counteracting the effects of fatty acids. The diphasic systemic process which results can be considered to represent an exaggeration of the processes which occur alternately and which, through normal oscillations, insure the dynamic systemic balance.

The adrenals conceivably control abnormal fatty acid activity by their quantitatively exaggerated intervention and by release of qualitatively abnormal products that would pass into the circulation and result in off balances. The activity of the adrenals in counteracting the influence exercised by fatty acids has been made the subject of a special investigation in our laboratories by E. F. Taskier.

By comparing the doses of an agent required to kill normal and adren alectomized animals, it has been possible not only to identify this intervention but to judge the degree of this specific defense mechanism. The "Adrenal Defense Index" for an agent—the ratio between the minimal lethal dose in normal animals and in adrenalectomized animals represents a numerical estimate of this response. It could be shown that for certain fatty acids, such as conjugated trienes, which are related to trauma, or alpha hydroxy fatty acids which are related to microbial invasion, a highly effective intervention of the adrenals occurs, through release of neogluco genic corticoids. The administration of neoglucogenic corticoids manifestly increases the resistance of the organism to the noxious effects of fatty acids. This influence is reduced for the mineralocorticoids and is nil for sodium chloride, otherwise an important factor related to adrenal intervention. (Note 17, Chapter VI)

We will discuss later an important difference, even an antagonism, between these two groups of corticoids when their influence is exerted concomitantly with that of other agents.