Endotoxin-stimulated human monocyte secretion of interleukin 1, tumour necrosis factor alpha, and prostaglandin E2 shows stable interindividual differences

Scand J Immunol. 1988 Jun;27(6):705-16. doi: 10.1111/j.1365-3083.1988.tb02404.x.


The secretions of interleukin 1 (IL-1), tumour necrosis factor alpha (TNF), and prostaglandin E2 (PGE2) of low-dose E. coli lipopolysaccharide (LPS)-stimulated human monocytes (M phi) were investigated in an endotoxin (ET)-free milieu (less than 1.6 pg LPS/ml). Human M phi cultures from nine healthy men were stimulated with 0, 12.5-500, and 250,000 pg LPS/ml as measured by a very sensitive Limulus test. The IL-1 activity was tested by the mouse costimulatory thymocyte (LAF) assay, which was thoroughly standardized and characterized (interassay variation 22-24%, intra-assay variation 3-7%). Spontaneous M phi secretions of IL-1, TNF, and PGE2 were negligible, but 12.5 pg LPS/ml significantly stimulated the secretions of these M phi products and the monokine responses to 500 and 250,000 pg LPS/ml were almost in the same range. It was demonstrated that the secretions of IL-1-TNF and TNF-PGE2 were strongly correlated. Pronounced interindividual differences in LPS responsiveness were demonstrated, and two low-responders, one of whom was HLA-DR1,2-positive, were identified. Three first-degree relatives of the DR1,2-positive low-responder had similar low responses. Furthermore, M phi cultures were prepared weekly for 4 weeks from four HLA-DR different men and the only DR2,2 homozygous individual had low monokine responses. In conclusion, stable interindividual differences in in vitro monokine and PGE2 secretions of LPS-stimulated M phi were demonstrated. It is suggested that HLA-DR2-positive individuals may be low responders.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biological Products / metabolism
  • Dinoprostone
  • Dose-Response Relationship, Drug
  • Endotoxins / pharmacology*
  • Female
  • HLA-DR Antigens / immunology
  • Humans
  • Interleukin-1 / metabolism*
  • Lipopolysaccharides / pharmacology
  • Macrophages / physiology*
  • Male
  • Monocytes / physiology*
  • Monokines
  • Prostaglandins E / metabolism*
  • Tumor Necrosis Factor-alpha / metabolism*


  • Biological Products
  • Endotoxins
  • HLA-DR Antigens
  • Interleukin-1
  • Lipopolysaccharides
  • Monokines
  • Prostaglandins E
  • Tumor Necrosis Factor-alpha
  • Dinoprostone