Influence of the regulatory peptide galanin on cytokine expression in human monocytes

Current research into neuropeptides is bringing to light many remarkable functions of these endocrine/neurocrine/paracrine factors, such as their roles in modulating immune responses. Galanin is a neuropeptide expressed in both neural and non-neural tissues and exerts its effects through three G protein-coupled receptors, GAL_1,2,3 -R. It has been demonstrated that galanin has modulatory effects on immune cells, including neutrophils and natural killer cells. Because monocytes express GAL₂ -R, and therefore are expected to be a target of galanin, we analyzed the effect of galanin on the expression of cytokines and chemokines by monocytes. Galanin increased the expression of IL-1β up to 1.5-fold, TNF-α, IL-10, IL-18, and CCL3 up to twofold, and CXCL8 up to fourfold in nonactivated monocytes, but had no major effect on activated monocytes. A cross-correlation analysis of cytokine expression profiles, irrespective of the activation status of the monocytes, revealed that galanin changed the cross-correlation of the expression of certain cytokines. Galanin abolished several significant correlations in IFN-γ-stimulated monocytes. For example, treatment with 10 nM galanin changed the Spearman's rank coefficient of IL-18 and CXCL8 from 0.622 (P ≤ 0.01) to 0.126. These results further emphasize the importance of neuroregulatory peptides, such as galanin and their therapeutic potential to treat inflammatory diseases.