PMID: 8590312Nov 1, 1995Paper

Neuropeptide regulation of cytokine expression: effects of VIP and Ro 25-1553

Journal of Interferon & Cytokine Research : the Official Journal of the International Society for Interferon and Cytokine Research
H TangD Ganea

Abstract

The neuropeptide VIP is present in high concentrations in normal lung, where it acts as a potent bronchodilator. VIP also downregulates T lymphocyte proliferation, possibly through its effect on cytokine expression. Although deficiencies in VIP levels are associated with asthma, VIP replacement therapy is impaired by its rapid degradation in the pulmonary microenvironment. A metabolically stable VIP peptide analog Ro 25-1553 has been developed and shown to act as a potent smooth muscle relaxant and suppressant of inflammatory cell accumulation. Proinflammatory cytokines play essential roles in inflammatory reactions. Here we compare the effects of VIP and Ro 25-1553 on IL-2, IL-4, and IFN-gamma production. Both VIP and Ro 25-1553 inhibit IL-2 and IL-4 but not IFN-gamma production and induce intracellular cAMP. Similar to VIP, Ro 25-1553 downregulates the IL-2 message and affects IL-4 production posttranscriptionally. Cytokines play important roles in allergic reactions, and increased cytokine levels are present in allergic asthmatic subjects. Therefore, downregulation of IL-2 and IL-4 production by Ro 25-1553 could play a significant role in the antiinflammatory activity of this peptide within the pulmonary microenvironment.

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Citations

Aug 1, 1996·Journal of Neuroimmunology·M C JohnsonD Ganea
Apr 9, 1998·Peptides·S YoshiharaS Watanabe
Feb 14, 2006·European Journal of Pharmacology·David A GronebergAxel Fischer
Oct 18, 2001·Pulmonary Pharmacology & Therapeutics·D A GronebergA Fischer
Jun 1, 2004·Pharmacological Reviews·Mario DelgadoDoina Ganea
Dec 26, 1996·Annals of the New York Academy of Sciences·H TangD Ganea
Feb 11, 1999·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·N Jabrane-FerratA E Goetzl

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