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Role of IFN-gamma and alpha in IL 1 synthesis and secretion of in vitro differentiated human macrophages: a
Abstract:
Human blood monocytes (Mo) cultured in vitro differentiate to macrophages (Mx) and lose the capacity to secrete interleukin 1 (IL 1) in response to endotoxin (LPS). Incubation of Mo with interferon gamma or alpha (IFN-gamma or IFN-alpha) prevented this loss of IL 1 secretory potential during the first 24 h of culture. However, there were marked differences between the two interferons if culture period was extended beyond 24 h. Incubation of Mo with IFN-gamma for 48 or 72 h induced IL 1 release in response to LPS in all the donors without exception. In contrast, 48-h incubation of Mo with IFN-alpha alpha caused IL 1 secretion (in response to LPS) in only a minority of donors, while 72-h incubation resulted in very little or no IL 1 release in all the individuals tested. Moreover, only IFN-gamma had the capacity to reinduce IL 1 secretory potential in Mx which had lost the capacity to secrete IL 1 during previous culture. These and other results suggest that IFN-alpha differs from IFN-gamma in being: a less potent IL 1 inducer, ineffective in maintaining IL 1 secretory capacity of fresh Mo for more than 48-72 h, completely unable to reinduce IL 1 secretory potential in culture-derived Mx. Thus, the two species of IFN appear to have a markedly different role in IL 1 synthesis and secretion.
Insights
Interferon-gamma (IFN-gamma) maintains interleukin-1 (IL-1) secretion in human monocytes (Mo) and macrophages (Mx) longer than interferon-alpha (IFN-alpha). IFN-gamma also reinduces IL-1 secretion in macrophages, unlike IFN-alpha.
Area of Science:
- Immunology
- Cell Biology
Background:
- Human blood monocytes (Mo) differentiate into macrophages (Mx) in vitro, losing their capacity to secrete interleukin-1 (IL-1) upon lipopolysaccharide (LPS) stimulation.
- Interferons (IFNs) are known to modulate immune responses, but their specific roles in regulating IL-1 secretion during monocyte-macrophage differentiation require clarification.
Purpose of the Study:
- To compare the effects of interferon-gamma (IFN-gamma) and interferon-alpha (IFN-alpha) on the IL-1 secretory potential of human monocytes and macrophages.
- To investigate the capacity of IFN-gamma and IFN-alpha to maintain or reinduce IL-1 secretion during in vitro culture.
Main Methods:
- Human monocytes were cultured in vitro and treated with either IFN-gamma or IFN-alpha for varying durations (24, 48, or 72 hours).
- The capacity of monocytes and differentiated macrophages to secrete IL-1 in response to LPS stimulation was assessed.
- Specific experiments were conducted to evaluate the ability of IFNs to reinduce IL-1 secretion in macrophages that had already lost this capacity.
Main Results:
- Both IFN-gamma and IFN-alpha initially prevented the loss of IL-1 secretory potential in monocytes within the first 24 hours.
- Extended incubation (48-72 hours) with IFN-gamma consistently induced IL-1 release in response to LPS across all donors.
- IFN-alpha showed limited efficacy in maintaining IL-1 secretion beyond 48 hours and was unable to reinduce IL-1 secretion in cultured macrophages.
Conclusions:
- IFN-gamma is more potent than IFN-alpha in maintaining and reinducing IL-1 secretory capacity in human monocytes and macrophages.
- The distinct effects of IFN-gamma and IFN-alpha suggest different roles in regulating IL-1 synthesis and secretion within the immune system.