P48 induces tumor necrosis factor and IL-1 secretion by human monocytes.
Bacterial products are potent stimulators of TNF and IL-1 release, however, the factors that regulate cytokine secretion in the absence of bacterial products are not well defined. P48 is a cytokine recently identified in the supernatant of the human null cell leukemia cell line Reh, which induces differentiation and cytolytic activity in HL-60 cells. P48 has been purified to homogeneity and is distinct from TNF-alpha TNF-beta, IFN-gamma, IL-6, and macrophage CSF. In the present study we examined the ability of P48 to stimulate cytokine release by human peripheral blood monocytes. P48 stimulated the secretion of TNF and IL-1 in a dose-dependent manner. Priming the monocytes with IFN-gamma enhanced P48-induced cytokine release but was not a requirement for secretion. Cytokine secretion was in response to P48 and was not caused by endotoxin contamination. The cytokine-inducing activity of P48 was extremely sensitive to heat treatment but could not be eliminated by using polymyxin B. Polyclonal antisera to P48 completely blocked the cytokine-inducing activity. P48 may be an important new member of the cytokine network involved in the regulation of cytokine secretion by monocytes.
Beezhold
D H
DH
Laboratory of Macrophage Biology, Guthrie Research Institute, Sayre, PA 18840-1692.
Leftwich
J A
JA
Hall
R E
RE
D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D005347:Fibroblasts / Q000187:drug effects; D006133:Growth Substances / Q000276:immunology / Q000502:physiology*; D006801:Humans; D007106:Immune Sera / Q000494:pharmacology; D007375:Interleukin-1 / Q000096:biosynthesis*; D007739:L Cells; D008070:Lipopolysaccharides / Q000494:pharmacology; D051379:Mice; D009000:Monocytes / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*
D006133:Growth Substances; D007106:Immune Sera; D007375:Interleukin-1; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha