Detection of macrophage inflammatory protein (MIP)-1 alpha and MIP-1 beta during experimental endotoxemia and human sepsis

Macrophage inflammatory protein (MIP)-1 alpha and MIP-1 beta regulate leuko cyte activation and trafficking, To assess the role of MIP-1 alpha and MIP- 1 beta in human inflammation, healthy subjects were studied during experime ntal endotoxemia with prior administration of ibuprofen, a cyclooxygenase i nhibitor, or dimeric p75 tumor necrosis factor (TNF)-alpha receptor, a TNF antagonist; septic patients were also studied. Following endotoxin, blood l evels of both MIP-1 molecules rose acutely and fell to baseline by 6 h (P = .001). While MIP-1 mediates fever in animals independent of cyclooxygenase blockade, in subjects given endotoxin and ibuprofen, MIP-1 levels increase d and fever was suppressed, MIP-1 levels were not diminished by inhibiting circulating TNF-alpha in humans. In septic patients, elevated levels of MIP -1 alpha and MIP-1 beta were detected within 24 h of sepsis and fell in par allel with TNF-alpha and interleukin-6 (P < .01). MIP-1 alpha and MIP-1 bet a increase during acute inflammation but are not associated with fever in e ndotoxemic humans during cyclooxygenase blockade.