Effect of substance P on production of interleukin-12 and interferon-gamma from peripheral blood mononuclear cells of chronic severe atopic dermatitis patients

Lim, Ji Hyun; Kang, Hoon; Park, Young Min; Cho, Sang Hyun; Lee, Seung Yeon

Abstract

BACKGROUND: In atopic patients, allergen-specific T cells express the Th2 phenotype. It is known that interleukin-12 (IL-12) is a major cytokine for the induction of Th1 responses and that a reduced release of IL-12 in atopic dermatitis patient is closely related to reduced production of interferon-gamma(INF-gamma). Recently, it has been reported that substance P (SP) positive nerve fibers express increased IL-12 and that elevated levels of this neuropeptide were seen in AD patients.
OBJECTIVE
This study was designed to examine the effects of SP and its fragment on the production of IL-12 and INF-gamma from peripheral blood mononuclear cells (PBMCs) of chronic severe atopic dermatitis (AD) patients, and moreover to establish neuro-immunomodulatory mechanisms in chronic severe AD patients. MATERIALS AND METHOD: The PBMCs from fifteen chronic severe AD patients and non-atopic individuals were stimulated with Staphylococcus aureus Cowan I strain. After stimulating the PBMCs, the effects of SP and SP fragments (SP1-4 and SP4-11) on the production of IL-12 and INF-gamma were analysed by enzyme-linked immunosorbent assay.
RESULTS
The levels of IL-12 and INF-gamma were significantly decreased in un-stimulated AD patients than in non-atopic controls. In chronic severe AD patients, SP and SP4-11 significantly increased the production of both IL-12 and INF-gamma compared to non-atopic controls. The enhancing effect of SP and SP4-11 was most significant at the concentrations of 10-8M and 10-6M. When the spantide, an SP antagonist, was added to SP and SP4-11 stimulated PBMCs, the productions of IL-12 and INF-gamma were downregulated in chronic severe AD patients but not in non-atopic controls. In contrast, SP1-4 fragment did not show any specific cytokine production.
CONCLUSION
These data suggests that SP and SP4-11, a carboxyl terminal of SP, are involved in the immunomodulation of chronic severe AD patient by regulating IL-12 and INF-gamma production, while SP1-4, an amino terminal of SP, has no effect on the cytokine production in AD patients.