Immunomodulatory potential of thymulin-Zn2+ in the alveolar epithelium: Amelioration of endotoxin-induced cytokine release and partial amplification of a cytoprotective IL-10-sensitive pathway

The immunomodulatory potential of thymulin in the perinatal epithelium is n ot web characterized. In an in vitro model of fetal alveolar type II epithe lial cells, we investigated the exhibition of an anti-inflammatory activity of this peptide hormone. Thymulin selectively ameliorated, in a dose-depen dent manner, the endotoxin-induced release of IL-1 beta (IC50 = 657 ng.ml(- 1)), but showed no inhibitory effect on IL-6 and TNF-alpha. Zinc, an anti-i nflammatory antioxidant, which is required for the biological activity of t hymulin, reduced the secretion of IL-1 beta (IC50 = 62 mu M), TNF-alpha (IC 50 = 1000 mu M), and, to a lesser extent, IL-6. This cation (100 mu M) ampl ified the effect of thymulin on IL-1 beta and TNF-alpha (IC50 < 0.1 ng.ml(- 1)), but not on IL-6. Analysis of whether thymulin is up-regulating a count erpart antiinflammatory signaling loop revealed the involvement of an IL-10 -sensitive pathway. These results indicate that thymulin acts as a novel du al immunoregulator by enhancing an anti-inflammatory cytoprotective respons e and depressing an inflammatory signal, an effect synergistically amplifie d, in part, by cationic zinc. (C) 2000 Academic Press.