Endotoxin‐Stimulated Human Monocyte Secretion of Interleukin 1, Tumour Necrosis Factor Alpha, and Prostaglandin E2 Shows Stable Interindividual Differences

Abstract

The secretions of interleukin 1 (IL‐1), tumour necrosis factor α (TNF), and prostaglandin E 2 (PGE 2) of low‐dose E. coli lipopolysaccharide (LPSJ‐stimulated human monocytes (Mø) were investigated in an endotoxin (ET)‐free milieu (<1.6 pg LPS/ml). Human Mø 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 Mø secretions of IL‐1, TNF, and PGE 2 were negligible, but 12.5 pg LPS/ml significantly stimulated the secretions of these Mø 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‐PGE 2 were strongly correlated. Pronounced interindividual differences in LPS responsiveness were demonstrated, and two low‐responders, one of whom was HLA‐DR 1,2‐positive, were identified. Three first‐degree relatives of the DR1.2‐positive low‐responder had similar low responses. Furthermore. Mø 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 PGE 2 secretions of LPS‐stimulated Mø were demonstrated. It is suggested that HLA‐DR2‐positive individuals may be low responders.