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Interleukin 6 (interferon beta 2) and interferon alpha/beta present in postendotoxin serum induce differentiation of
D H Pluznik1, N Frappier, R P Nordan
1Division of Cytokine Biology, Food and Drug Administration, Bethesda, MD 20892.
Abstract:
Serum from lipopolysaccharide-treated mice (postendotoxin serum, PES) induces the differentiation of M1 myeloid leukemia cells into mature macrophages, as well as supporting the proliferation of the interleukin 6 (IL6)-dependent B9 hybridoma cells. The kinetics of appearance of these two activities in PES were identical. To determine whether these two activities are due to the presence of the same substance, we tested whether anti-IL6 antibodies could neutralize the differentiation-inducing activity of PES. We found that anti-IL6 antibodies completely neutralized the proliferation of B9 cells and resulted in a 60% neutralization of the differentiation-inducing activity of PES. Anti-interferon alpha/beta (INF alpha/beta) antibodies neutralized 70% of the differentiation-inducing activity of PES. These data suggest that the differentiation-inducing activity of PES is not limited to IL6, and that PES contains additional factors such as INF alpha/beta that are capable of inducing differentiation of M1 cells.
Insights
Postendotoxin serum (PES) from treated mice promotes macrophage differentiation and hybridoma cell proliferation. While interleukin 6 (IL6) drives proliferation, other factors like interferon alpha/beta (INF alpha/beta) also contribute to differentiation.
Area of Science:
- Immunology
- Cell Biology
- Molecular Biology
Background:
- Postendotoxin serum (PES) from lipopolysaccharide-treated mice exhibits dual activities: inducing M1 myeloid leukemia cell differentiation into macrophages and supporting interleukin 6 (IL6)-dependent B9 hybridoma cell proliferation.
- The temporal appearance of these two activities in PES is identical, prompting investigation into a common causative agent.
Purpose of the Study:
- To determine if the differentiation-inducing and proliferation-supporting activities in PES are mediated by the same substance.
- To identify the specific factors within PES responsible for M1 cell differentiation.
Main Methods:
- Neutralization assays using antibodies against IL6 and interferon alpha/beta (INF alpha/beta).
- Assessment of M1 cell differentiation and B9 cell proliferation following PES treatment and antibody incubation.
Main Results:
- Anti-IL6 antibodies completely neutralized B9 cell proliferation.
- Anti-IL6 antibodies neutralized 60% of the differentiation-inducing activity of PES.
- Anti-INF alpha/beta antibodies neutralized 70% of the differentiation-inducing activity of PES.
Conclusions:
- The differentiation-inducing activity of PES is not solely attributable to IL6.
- PES contains additional factors, including INF alpha/beta, that contribute to M1 cell differentiation.
- These findings highlight the complex nature of immune modulation by endotoxin-induced serum factors.