Effect of gamma interferon and interleukin 10 on phosphoinositol turnover by human neutrophils in vitro

We evaluated the levels of inositolmono-(IP1), di(IP2), tri-(IP3) and tetraphosphates (IP4) in human neutrophils (N) stimulated with gamma interferon (IFN-gamma) (200 microliters from a pool of cell culture supernatant obtained from 1 x 10(7) PHA-primed peripheral blood mononuclear cells (30-60 min at 37 degrees C, 5% CO2)) in the presence of in the absence of interleukin 10 (IL-10) (10 micrograms/10 microliters). The results, reported as mean +/- SEM cpm, showed that IFN-gamma induced a significant increase only in the IP3 level (N + medium = 1,413 +/- 172 and N + IFN-gamma = 8,875 +/- 832). However, this activation mediated by IFN-gamma was blocked partially in the presence of IL-10 (N + IFN-gamma + IL-10 = 2,430 +/- 239) (P < 0.05). Interleukin 10 alone did not induce significant alterations in the content of IP1 (1,203 +/- 123), IP2 (1,880 +/- 163), IP3 (938 +/- 102) or IP4 (2,403 +/- 345) when compared to the respective controls in the absence of IL-10 (IP1 = 1,625 +/- 132; IP2 = 1,343 +/- 149; P3 = 1,413 +/- 172 and IP4 = 3,281 +/- 234). We also demonstrated the inhibitory effect of IL-10 of chemoluminescence generation by human neutrophils during phagocytosis of opsonized particles (OZ). Chemoluminescence generation was enhanced by IFN-gamma (N = OZ = 42.8 +/- 3.9 and N + OZ + IFN-gamma = 66.5 +/- 4.3) and this effect was reduced by IL-10 (N + OZ + IFN-gamma + IL-10 = 37.6 +/- 5.1). These data suggest that IL-10 modulates the neutrophil response and may be important for the development of new treatments of inflammatory injury.