Dose-response effect of in vivo administration of endotoxin on polymorphonuclear leukocytes oxidative burst.

In vitro, endotoxin primes polymorphonuclear leukocytes (PMNs) to respond with a greater oxidative burst. The purpose of the present study was to investigate the in vivo effect of a wide range of single endotoxin bolus doses using a rat model. PMNs were subsequently challenged in vitro with phorbol ester to produce reactive oxygen intermediates (ROI). Flow cytometric determination of ROI production by large doses induced a decrease in ROI production by the few PMNs that remained in the circulation. By 6 h after injection, ROI production had returned to basal levels after a high dose, and was still increasing after a low dose. Neutropenia occurred immediately after endotoxin injection. After 6 h, PMN counts returned to almost normal levels with a high dose, but rebound neutrophilia occurred with a small dose. In contrast to in vitro studies, in vivo injection showed a response pattern that varied widely with dose and time of observation.

Dialysable nonspecific inhibitor of lymphocyte proliferation related to E-receptors (CD2).

Several investigators have pointed out that lymphocytic function may be profoundly affected by soluble factors occurring in human serum. It was observed, previously, that the addition of normal human serum dialysate (NHSD), at the beginning of lymphocyte cultures, inhibited the proliferative response to phytohemagglutinin (PHA) and to allogeneic cells. This suppressive effect was removed by previous absorption of NHSD with sheep erythrocytes (E). These data suggested that the dialysable fraction of human serum contains a suppressive factor, apparently related to the human T cell receptor for E (T11 or CD2). In this study we investigated at which phase of the proliferative response does the inhibition induced by NHSD take place. In order to confirm the relationship between this inhibitory factor and E-receptors, the NHSD was subjected to passage through a sepharose affinity column sensitized with an anti-E-receptor serum. This anti-E-receptor serum was obtained by immunizing a sheep with autologous E sensitized with human E-receptors. Time-course experiments showed that NHSD inhibited lymphocyte proliferation induced by PHA even when added to the cultures 18-24 h after mitogenic stimulation. In bidirectional mixed lymphocyte cultures the impairment of the proliferative response was inversely proportional to the time of NHSD addition. NHSD also inhibited the interleukin-2 (IL2) mediated proliferation of lymphoblasts previously exposed to PHA to ensure IL-2-receptors expression. The inhibitory effects of the NHSD were completely removed by absorption with E or by passing NHSD through the affinity column sensitized with the anti-E-receptor serum.(ABSTRACT TRUNCATED AT 250 WORDS)