BIOLOGICAL SIGNIFICANCE OF ELEVATED TNF LEVELS - IN-VIVO ADMINISTRATION OF MONOCLONAL-ANTIBODY AGAINST TNF FOLLOWING HEMORRHAGE SHOCK INCREASES THE CAPACITY OF MACROPHAGES TO RELEASE TNF WHILE RESTORING IMMUNORESPONSIVENESS

Haemorrhagic shock results in a severe depression of the cellular and humoral immunity, thus rendering the host increasingly susceptible to sepsis. To study the effect of elevated TNF release following haemorrhagic shock on depressed macrophage and splenocyte functions, C3H/HeN mice were pretreated intraperitoneally with either anti-murine TNF-Ab or saline. Twenty hrs later, mice were bled to and maintained at a mean BP of 35 mmHg for 60 min followed by adequate fluid resuscitation. Pretreatment with anti-TNF-Ab completely neutralized elevated TNF plasma levels following haemorrhage. This was associated with an increased (P < 0.05) capacity of pM phi isolated 24 h after haemorrhagic shock to release TNF, while the ability to secrete IL-6 and PGE(2) was reduced. Haemorrhagic shock-induced suppression of pM phi antigen presentation capacity and MHC class II antigen expression, as well as depression of splenocyte proliferation and lymphokine production was also attenuated (P < 0.05) by anti-TNF-Ab pretreatment. These data indicate that elevated circulating TNF levels play a pivotal role in the depression of essential macrophage and splenocyte functions following haemorrhagic shock.