Enhancement of tumour necrosis factor production and sensitivity to interleukin-2 of human peripheral blood mononuclear cells stimulated by lipopolysaccharide and muramyl dipeptide in vitro.
The effect of lipopolysaccharide, muramyl dipeptide, and a combination of these agents in vitro on the production of tumour necrosis factor (TNF) by human peripheral blood mononuclear cells (PBMC; monocytes and lymphocytes) and on the sensitivity of these cells to recombinant interleukin-2 (IL-2) was studied. Both lipopolysaccharide and muramyl dipeptide, alone and combined, induced the production of TNF alpha by blood monocytes and lymphocytes, although the T-cells made only a very small contribution to the TNF produced by the lymphocyte fraction, most being produced by the B-cells. The B-lymphocytes and monocytes also spontaneously produced TNF alpha. Pretreatment of the mononuclear cells with a combination of lipopolysaccharide and muramyl dipeptide, but not with each preparation separately, led to enhancement of the proliferative response of these cells to recombinant IL-2. Incubation of mononuclear cells with muramyl dipeptide, muramyl dipeptide plus lipopolysaccharide, and to a lesser extent with lipopolysaccharide alone led to the generation of more-active lymphokine-activated killer cells in the presence of IL-2 than when IL-2 was used alone. The resultant lymphokine-activated killer cells lysed both human and murine tumour target cells.
Rakhmilevich
A L
AL
Research Institute of Human Morphology, Academy of Medical Sciences of the USSR, Moscow.
Shneiderova
M A
MA
Korobko
V G
VG
Chuvpilo
S A
SA
D000119:Acetylmuramyl-Alanyl-Isoglutamine / Q000494:pharmacology; D002455:Cell Division; D006801:Humans; D066298:In Vitro Techniques; D007376:Interleukin-2 / Q000494:pharmacology*; D015979:Killer Cells, Lymphokine-Activated / Q000276:immunology; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000276:immunology*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008214:Lymphocytes / Q000276:immunology; D009000:Monocytes / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*
D007376:Interleukin-2; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D000119:Acetylmuramyl-Alanyl-Isoglutamine