Immunomodulatory potential of thymulin-Zn(2+) 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 not well characterized. In an in vitro model of fetal alveolar type II epithelial cells, we investigated the exhibition of an anti-inflammatory activity of this peptide hormone. Thymulin selectively ameliorated, in a dose-dependent manner, the endotoxin-induced release of IL-1 beta (IC(50) = 657 ng. ml(-1)), but showed no inhibitory effect on IL-6 and TNF-alpha. Zinc, an anti-inflammatory antioxidant, which is required for the biological activity of thymulin, reduced the secretion of IL-1 beta (IC(50) = 62 microM), TNF-alpha (IC(50) = 1000 microM), and, to a lesser extent, IL-6. This cation (100 microM) amplified the effect of thymulin on IL-1 beta and TNF-alpha (IC(50) < 0.1 ng. ml(-1)), but not on IL-6. Analysis of whether thymulin is up-regulating a counterpart anti-inflammatory signaling loop revealed the involvement of an IL-10-sensitive pathway. These results indicate that thymulin acts as a novel dual immunoregulator by enhancing an anti-inflammatory cytoprotective response and depressing an inflammatory signal, an effect synergistically amplified, in part, by cationic zinc.
Oxygen Signaling Group, Tayside Institute of Child Health, Dundee, Scotland, DD1 9SY, United Kingdom. j.j.haddad@dundee.ac.uk
J J
JJ
Haddad
S C
SC
Land
N E
NE
Saadé
B
B
Safieh-Garabedian
D000276:Adjuvants, Immunologic / Q000378:metabolism* / Q000494:pharmacology; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000378:metabolism / Q000494:pharmacology; D016207:Cytokines / Q000096:biosynthesis / Q000378:metabolism*; D019610:Cytoprotection / Q000187:drug effects / Q000276:immunology; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation / Q000187:drug effects; D004357:Drug Synergism; D004731:Endotoxins / Q000494:pharmacology; D004847:Epithelial Cells / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D007375:Interleukin-1 / Q000096:biosynthesis; D016753:Interleukin-10 / Q000378:metabolism*; D015850:Interleukin-6 / Q000096:biosynthesis; D011650:Pulmonary Alveoli / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects / Q000276:immunology; D013935:Thymic Factor, Circulating / Q000378:metabolism* / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis; D015854:Up-Regulation / Q000187:drug effects; D015032:Zinc / Q000378:metabolism* / Q000494:pharmacology
D000276:Adjuvants, Immunologic; D000893:Anti-Inflammatory Agents; D016207:Cytokines; D004731:Endotoxins; D007375:Interleukin-1; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D013935:Thymic Factor, Circulating; D015032:Zinc