Kupffer cells (KC), by virtue of their ability to present antigen (AP) and 
express major histocompatibility complex (MHC) class II antigen (Ia), play a 
pivotal role in the host defence system against invading micro-organisms. 
Although haemorrhagic shock depresses the above KC functions, it is not known 
whether increased KC tumour necrosis factor (TNF) production and elevated TNF 
plasma levels following haemorrhage are responsible for it. To study this, 
C3H/HeN mice were pretreated intraperitoneally with either anti-murine TNF 
antibody (anti-TNF Ab) or saline. Twenty hours later mice were bled and 
maintained at a mean blood pressure of 35 mmHg for 60 min followed by adequate 
fluid resuscitation. Two and 24 hr later, plasma was collected and KC were 
isolated. AP was measured by co-culturing KC with the D10.G4.1 Th cell clone. Ia 
expression was determined by direct immunofluorescence. Interleukin (IL)-1, IL-6 
and TNF levels in KC supernatants and plasma were measured with bioassays or 
ELISA. Haemorrhage increased circulating TNF levels by 215% at 2 hr and by 76% 
at 24 hr (P less than 0.05), which was prevented by pretreatment with anti-TNF 
Ab. Haemorrhage-induced increase of circulating IL-6 was abolished (P less than 
0.05) at 2 hr but not at 24 hr in the anti-TNF Ab group. The suppression of KC 
AP (P less than 0.05) and Ia expression (P less than 0.05) due to haemorrhage 
was attenuated (P less than 0.05) in anti-TNF Ab-treated mice at 2 and 24 hr and 
KC IL-1 and TNF synthesis was further (P less than 0.01) increased. These 
results indicate that TNF plays a critical role in the initiation and regulation 
of KC AP, Ia expression, and cytokine production following haemorrhage.