IL-4 INDUCES CAMP AND CGMP IN HUMAN MONOCYTIC CELLS

HUMAN monocytes, preincubated with IFN-gamma, respond to IL-4 by a cGM P increase through activation of an inducible NO synthase. Here, IL-4 was found to induce an accumulation of cGMP (1 - 3 min) and cAMP (20 - 25 min) in unstimulated monocytes. This was impaired with NOS inhibit ors, but also with EGTA and calcium/calmodulin inhibitors. These resul ts suggest that: (1) IL-4 may stimulate different NOS isoforms in rest ing and IFN-gamma activated monocytes, and (2) cAMP accumulation may b e partially dependent on the NO pathway. By RT-PCR, a type III constit utive NOS mRNA was detected in U937 monocytic cells. IL-4 also increas ed the [Ca2+](i) in these cells. Different NOS may thus be expressed i n monocytic cells depending on their differentiation and the signals t hey receive.