Regulation of in vitro human leukocyte interferon production: effect of prostaglandin synthetase and phosphodiesterase inhibition.

A great variability exists in the in vitro capability of peripheral blood leukocytes (PBL) of apparently healthy adults to produce IFN-alpha. In this report, we have studied the effects of prostaglandins, indomethacin and pentoxifylline upon IFN-alpha production by the PBL of normal healthy donors. The donors were divided into two groups: "normal producers" - donors that consistently produced greater than 2,000 ref. units IFN-alpha per 10(7) PBL and "low producers" - donors that consistently produced less than 2,000 ref. units IFN-alpha per 10(7) PBL. Addition of exogenous PGE1 or PGE2 into interferon production media significantly inhibited IFN-alpha yield by the PBL of both normal and low producers. The inhibition was dose dependent. A significant rise in the IFN-alpha yield was seen when PBL of "low producers" were exposed individually to either pentoxifylline or indomethacin. However, no increase in titer of IFN-alpha was seen when PBL of "normal producers" were exposed to either of these two agents during interferon production periods. With regard to PBL of "low producers", the enhancement of IFN-alpha yield was further potentiated when both indomethacin and pentoxifylline were utilized concurrently at their optimal concentrations. These results suggest that enhancement of IFN-alpha production by PBL of apparently healthy adults who are low producers may be possible and may have preventive value.