Defective macrophage antigen presentation following haemorrhage is associated with the loss of MHC class II (Ia) antigens.

Although recent studies indicate that severe and prolonged haemorrhage, despite adequate fluid resuscitation, induces profound depression of cell-mediated immunity, the mechanism of this remains unknown. Since macrophages (M phi) play a key role in the development of a competent immune response by the presentation of antigens, the study investigated (i) whether the capacity of the M phi to present antigen is altered even following mild hypotension, and (ii) what effects do different degrees of hypotension have on the M phi-mediated processes associated with antigen presentation (i.e. the expression Ia antigen, membrane-associated IL-1 or the secretion of IL-1). The results indicate that a minimal drop in blood pressure to approximately 50 mmHg (1 hr duration) was sufficient to depress M phi antigen presentation (AP). Similarly, even a transient hypotensive episode of 15 min duration at 35 mmHg was sufficient to produce a pronounced decline in AP. Decreased AP was observed as early as 12 hr after the haemorrhagic episode (35 mmHg; 1 hr) and remained detectable for at least 120 hr thereafter. The reductions in AP capacities were qualitatively similar in both peritoneal and splenic populations, and were not attributable to surgical stress, heparinization or ether anaesthesia. Determination of IL-1 production, as well as membrane-bound IL-1 levels, in these cell populations showed no significant difference from controls. However, a significant decrease was observed in the percentage of Ia antigen (MHC class II)-positive M phi, suggesting that reduced AP following haemorrhage may be related to the inability of these cells to express Ia.