Interferon‐gamma induced proliferation of human myeloid leukaemia cell lines

Interferon‐gamma (IFN‐γ) is a pleiotropic cytokine involved in the regulation of various phases of immune and inflammatory responses; it also has anti‐viral and anti‐proliferative activity. Using continuous human leukaemia cell lines as model systems, we found that IFN‐γ stimulated the proliferation of leukaemic myeloid cells; this effect was specifically neutralized by an anti‐IFN‐γ monoclonal antibody (McAb). No proliferative response was seen in autonomously growing cell lines; however, 11/19 constitutively growth factor‐dependent cell lines showed a significant response in short‐term proliferation assays upon incubation with IFN‐γ. The stimulation indices ranged from 2 to 37 compared with the untreated control cells; the EC50 values for these cell lines were in the range of 0.1–0.6 ng/ml IFN‐γ. Flow cytometric analysis demonstrated heterogeneity in the expression of the IFN‐γ receptor, as it was found on 37–97% of the cells per cell line. The effects of IFN‐γ on proliferation triggered by a spectrum of 10 other cytokines were variable, and both stimulation and attenuation of the proliferative responses were seen in different cell lines. Under serum‐free culture conditions, IFN‐γ acted as a survival factor suppressing apoptosis. As has been described for other functional processes triggered by IFN‐γ, the proliferation‐inducing activity of IFN‐γ also led to activation of the signal transducing element STAT 1. Thus, IFN‐γ can induce myeloid leukaemia cells to proliferate and can modulate their proliferative response to other cytokines. Therefore IFN‐γ may be a pathologically relevant ligand for leukaemic cell proliferation in vivo . In physiological settings, IFN‐γ might be a bifunctional regulator of haemopoietic cell proliferation, depending on other differential co‐signals from the micro‐environment.