DIFFERENT RESPONSES OF PLASMA ACTH AND CORTICOSTERONE AND OF PLASMA INTERLEUKIN-1-BETA TO SINGLE AND RECURRENT ENDOTOXIN CHALLENGES

In a parallel study in 10 individual rats, three time series of plasma concentrations of ACTH, corticosterone (CORT), and interleukin-1 beta (IL-1 beta) were measured before (time 0) and at intervals between 15 and 480 mill following intra-arterial (i.a.) infusions of 25 mu g/kg lipopolysaccharide (LPS), All LPS injections were given at 9 AM, The f irst time series was performed on naive rats (day 1), A sequence of si x daily injections (days 3-8) of the same dose of LPS followed, The po st-LPS time course of the plasma ACTH, CORT and IL-1 beta levels were studied on days 3 (second injection) and 8 (seventh injection), The fi rst LPS injection induced a rapid (30 min) eightfold rise in plasma AC TH and CORT, culminating in concentrations 30 times the baseline at 60 min (ACTH) and 15 times baseline at 120 min (CORT), Both hormones rec eded back to the initial basal level at 480 min, On the other hand, IL -1 beta increased slowly to peak at 13 times baseline 120 min before d eclining to minimal seven- to ninefold basal levels, 480 min and even 48 h post-LPS, During the second phase of the experiment starting 48 h after the initial LPS priming sequence, the ACTH and CORT responses t o daily recurrent LPS injections again differed from those of IL-1 bet a. The post-LPS time courses of the ACTH and CORT reaction displayed a typical pattern of a progressive attenuation studied at days 3 and 8, The peak amplitudes at days 3 and 8 were reduced to 60 and 10%, respe ctively, for ACTH, and to 85 and 45% for CORT of those observed at the first LPS test, The duration of the response (both) was also shortene d from 480 min (first LPS test) to 300 min at days 3 and 8, The post-L PS patterns of the IL-1 beta responses were characterized, first by ba sal levels seven to nine times higher than the initial baseline values (day 1), and by a rapid suppression of the post-LPS response, with on ly a slight (30%) increase at day 3 and no increase at day 8, Thus, af ter both acute and recurrent LPS administration, ACTH/CORT and IL-1 be ta reacted differently to the endotoxin challenge. The two LPS reactiv e systems were not correlated, This is inconsistent with the often pro posed role of increased plasma IL-1 beta release as an intermediary fa ctor in the LPS-induced recruitment of the corticotropic axis in gener al infections.