Science and Education Publishing American Journal of Medical and Biological Research 1 1 2013 05 07 The Anti-Inflammatory and Immunomodulatory Activity of Thymulin Peptide is NF-κB-Dependent and Involves the Downregulation of IκB-α 41 49 EN John J. Haddad Department of Medical Laboratory Technology, Faculty of Health Sciences, Beirut Arab University, Beirut, Lebanon Lama H. Hanbali AJMBR2013122 10.12691/ajmbr-1-2-2 2012 11 29 2013 04 26 2013 05 07 The immunomodulatory activity of thymulin and related analogues in vivo is not well characterized in the CNS. We have previously provided evidence for an anti-inflammatory potential of thymulin in downregulating proinflammatory cytokines in a NF-κB-dependent mechanism in vitro. Furthermore, we have shown that intracerebroventricular (ICV) treatment with thymulin in the hippocampus (HC) reduced the nuclear localization and activation of NF-κB, an effect mediated by the IκB-¦Á/pIκB- ¦Á pathway in vivo. ICV stereotaxic injection of endotoxin (ET) differentially upregulated the nuclear translocation /expression of NF-κB₁ (p50), NF-κB₂ (p52), RelA (p65), RelB (p68) and c-Rel (p75) in the HC. Pretreatment with thymulin followed by ET exposure reduced the nuclear translocation of NF-κB subunits. The anti-inflammatory effect of thymulin seems to be mediated via the IκB-α pathway since thymulin downregulated ET-induced phosphorylation of IκB-α. Stereotaxic pretreatment with synthetic peptide analogue of thymulin (PAT) reduced the nuclear translocation of NF-κB subunits, an effect mediated by downregulating the phosphorylation of IκB-α. EMSA revealed dose-dependent inhibition of NF-κB/DNA activation mediated by ICV ET. These results indicate that the anti-inflammatory effect of thymulin/PAT, mediated by IκB-α, is NF-κB-dependent and involves the downregulation of the nuclear translocation of various NF-κB subunits and their subcellular activation.