[Effects of DbcAMP on tumor necrosis factor and interleukin-1 production in human monocytes]

Recent reports have shown that dibutyryl cAMP (DbcAMP) blocks endotoxin-induced lung injury. To determine whether DbcAMP suppresses the production of tumor necrosis factor (TNF) and interleukin-1 (IL-1) in human monocytes, we measured the levels of TNF and IL-1 in response to E. Coli lipopolysaccharide (40 micrograms.ml-1) in vitro. We now show that DbcAMP suppressed dose-dependently the production of TNF in human monocytes, and DbcAMP totally suppressed it at the dose above 5 x 10(-4) M. However, DbcAMP did not suppress the production of IL-1 even at the dose of 5 x 10(-3) M in human monocytes. These data suggest that the productive mechanism of IL-1 may be different from that of TNF. Further, suppression of TNF by DbcAMP may contribute to the beneficial effects in animal models of septic shock or lung injury and this may have clinical implications.