Cytokine Production by Monocytes during Sepsis

The production by monocytes of interleukin-la (IL-la), interleukin-1lj# (IL-1,), interleukin-6 (IL-6), and tumor necrosis factor alpha (TNFa) in intensive care unit (ICU) patients with sepsis syndrome (n = 23) or noninfectious shock (n = 6) is reported. Plasma cytokines, cell-associated cytokines within freshly isolated monocytes and LPS-induced in vitro cytokine production were assessed at admission and at regular intervals during ICU stay. TNFa and IL-6 were the most frequently detected circulating cytokines. Despite the fact that IL-la is the main cytokine found within monocytes upon in vitro activation of cells from healthy individuals, it was very rarely detected within freshly isolated monocytes from septic patients, and levels of cell-associated IL-1,@ were lower than those of TNFa. Cell-associated IL-1,6 and TNFa were not correlated with corresponding levels in plasma. Upon LPS stimulation, we observed a profound decrease of in vitro IL-la production by monocytes in all patients, and of IL-1if, IL-6, and TNFa in septic patients. This reduced LPS-induced production of cytokines was most pronounced in patients with gram-negative infections. Finally, monocytes from survival patients, but not from nonsurvival ones recovered their capacity to produce normal amounts of cytokines upon LPS stimulation. In conclusion, our data indicate an in vivo activation of circulating monocytes during sepsis as well as in noninfectious shock and suggest that complex regulatory mechanisms can downregulate the production of cytokines by monocytes during severe infections. (J. Clin. Invest. 1991. 88:1747-1754.)