Injection of lyophilized granuloma pouch exudate inhibited the formation of cotton pellet granulomas in rats. In contrast, lyophilized serum, obtained from rats bearing granuloma pouches, did not exert measurable anti-inflammatory effects. The antiphlogistic activity was not dependent upon the time of pouch development at which the exudates were harvested, and thus did not appear to be derived from the systemic circulation. Unlike ACTH, the exudates failed to elevate plasma-corticosteroid levels in hypophysectomized rats. The exudates exerted significant anti-inflammatory activity in adrenalectomized rats, and these effects were enhanced by concomitant treatment with small doses of whole adrenocortical extract (ACE). The exudates themselves contained little or no corticosterone or cortisol. Thus, the anti-inflammatory properties of pouch exudates do not appear to depend upon contained ACTH or adrenalcorticoids. In contrast to glucocorticoids, anti-inflammatory doses of exudate had no adverse effect on body weight gain. This fact, together with the observed synergism of exudate and ACE in reducing inflammation, suggests that the mechanisms of action of exudate and glucocorticoids may be different.
Lyophilized granuloma pouch exudates obtained from intact or adrenalectomized rats contain an anti-inflammatory substance active parenterally in the cotton pellet and in the granuloma pouch methods. In these crude preparations the activity is only a small fraction of that of cortisone acetate. Both exudates are active in hypophysectomized animals but not in adrenalectomized animals. It appears that the active fraction is not itself an adrenal steroid, but it is possible that small amounts of adrenal hormones act as conditioning factors for the anti-inflammatory activity. The release of a nonadrenal anti-inflammatory substance during inflammation would help explain some anergic phenomena; such a substance could also be involved in limiting and terminating the inflammatory process.
In the adrenalectomized rat placed on a regular diet, neither ammoniated glycyrrhizin nor licorice was able to prolong survival time beyond that of the controls while desoxycorticosterone acetate (DCA) was very effective. When adrenalectomized rats were maintained on saline, it was observed that only DCA caused significant polydipsia, arterial hypertension and cardiovascular lesions; ammoniated glycyrrhizin and licorice were practically inactive, in contrast to their previously reported activity in the normal rat. The presence of the adrenal glands appears necessary to the renal cardiovascular effects of these extracts and it seems that the observed activity is mediated through these glands and that neither ammoniated glycyrrhizin nor licorice possesses direct DCA-like or mineralocorticoid properties.
A method has been developed for the estimate of total tissue sodium by direct measurement of radiosodium concentrations in undigested samples. Accuracy is comparable to that of flame photometric estimates on tissue digests; time and cost, about one-quarter as great. The method appears particularly useful for experimental designs requiring multiple tissue sodium measurements.
SUMMARY
The reversal of cortisone action on formaldehyde arthritis reported by Csaba, Törő, Horváth, Ács & Mold (1962) after thymectomy in the rat did not occur using either the cotton pellet, the granuloma pouch or the acute paw-oedema procedures. Thymectomy alone caused a reduction of inflammation in both the cotton pellet and the granuloma pouch methods but had no effect on acute formaldehyde-induced paw-oedema. It is concluded that the thymus is not essential for the anti-inflammatory activity of cortisone.
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