Pretreatment of murine macrophages with interferon (IFN) influences a variety of their responses to other mediators. For example, bone marrow derived macrophage progenitors pretreated with IFN α + β display augmented proliferation upon subsequent exposure to specific macrophage-type colony-stimulating factor (M-CSF). Similar pretreatment of macrophage-enriched cultures from proteose-peptone elicited peritoneal exudate cells results in enhanced- production of the immunoregulatory polypeptide interleukin 1 (lL-1) in response to lipopolysaccharide (LPS). Therefore, the present investigation was performed to determine if exposure of mature murine exudate macrophages and macrophage cell line cultures would, in addition, augment M-CSF stimulated IL-1 production. The results indicate that preincubation with IFN α + β enhances IL-1 production in response to M-CSF as well as to LPS. This pretreatment regimen elicited enhanced macrophage responsiveness to sub—optimal doses of CSF as well as LPS.

LPS hyporesponsive cells from C3H/HeJ mice or CSF hyporesponsive P388Di monocytic tumor cells produced an apparently synergistic level of IL-1 in response to the two stimuli combined. Prior exposure to IFN α + β enhanced this apparently synergistic response.

An unexpected finding in this investigation was that IFN α + β pretreatment dosages exceeding 1000 U/ml directly stimulated IL-1 production by exudate macrophages. Direct and augmented stimulation of IL-1 production by IFN α + β could be neutralized by addition of highly specific anti IFN α + β antiserum or by heat treating the preparation at 56°C for 45 minutes.

There is a correlation between the local presence of IFN and both inflammation and fever. This observation is discussed in regard to the IFN enhanced production of IL-1.