INHIBITORY EFFECT OF GROWTH-HORMONE ON TNF-ALPHA SECRETION AND NUCLEAR FACTOR-KAPPA-B TRANSLOCATION IN LIPOPOLYSACCHARIDE-STIMULATED HUMAN MONOCYTES

Several studies have pointed to a link between immune and endocrine sy stems, including a regulatory function of GH on monocyte activation. T he present study demonstrates that human THP-1 promonocytic cells, eng ineered by gene transfer to constitutively produce human growth hormon e (hGH), secreted depressed amounts of TNF-alpha in response to challe nge by LPS. The effect of GH appears to occur in an autocrine fashion, since the inhibitory effect on TNF-alpha secretion by constitutive GH production could be abolished in the presence of anti-hGH mAb. The GH -induced inhibitory effect was also observed using normal human monocy tes and monocyte-derived macrophages. Inhibition of TNF-alpha producti on by THP-1-hGH-transfected cells cultured in the presence of LPS is d ependent on a selective pathway, since no inhibition of TNF-alpha prod uction was observed when cells were cultured in the presence of PMA. I nhibition of TNF-alpha secretion by LPS-stimulated THP-1-hGH cells was associated with a decrease in nuclear translocation of nuclear factor -kappa B. The capacity of GH to inhibit LPS-induced TNF-alpha producti on by monocytes without altering other pathways leading to TNF-alpha p roduction may be of potential relevance in septic shock, since GH is a vailable for clinical use.