CYTOKINE GENE-EXPRESSION IN HUMAN LPS-STIMULATED AND IFN-GAMMA-STIMULATED MONONUCLEAR-CELLS IS INHIBITED BY HEPARIN

In addition to its well-understood anticoagulant activity. heparin is known to modulate a variety of biological functions including immunolo gic responses. In order to investigate whether heparin influences the humoral immunity by interacting with cellular elements and affecting g ene expression in blood circulating cells, we studied the effect of he parin on IL-1 beta, IL-6 and TNF alpha mRNAs in human lipopolysacchari de-(LPS)- or interferon-gamma(IFN gamma)-stimulated mononuclear ells. The study of mRNA was carried out by an initial PCR screening followed by a Northern blot quantitative analysis. Heparin (0.5 U/ml) turned o ut to inhibit all three cytokine gene expressions. The mRNA decrease w as 37 +/- 6% for IL-1 beta, 53 +/- 3% for IL-6 and 47 +/- 4% for TNF a lpha with LPS stimulus. No differences could be observed in the inhibi tory effect of heparin on IFN gamma-stimulated cells. This effect of h eparin was confirmed in a subset of experiments performed on purified monocytes. These results suggest an important immunosuppressive effect of heparin on cell-mediated immune responses.