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Substance P (SP) induces increased vascular permeability, vasodilatation and granulocyte infiltration upon intradermal injection. Studies with antagonists and mast cell-deficient mice have suggested that granulocyte infiltration in response SP is mediated by leukotriene (LT) B4 derived from mast cells. However, the release of LTB4 has not been detected using mast cells isolated from human skin. Here we report the release of LTB4, prostaglandin (PG) D2 and histamine from guinea pig skin tissue in response to SP. The release of these agents occurred in a dose-dependent manner over a concentration range of SP from 1 x 10(-6) to 3 x 10(-4) M. No detectable PGE2 was released at any concentration up to 3 x 10(-4) M SP. The kinetics of histamine release induced in response to SP was more rapid than that induced by antigen. By comparison, SP-induced and antigen-induced release of LTB4 and PGD2 were similar, but slower than the histamine release. In the absence of extracellular Ca2+, release of histamine and PGD2 in response to SP was partially impaired, but to a lesser extent than that induced by antigen. On the other hand, LTB4 release in response to both SP and antigen was abolished under the same conditions. These results indicate that SP induces the release of LTB4, as well as histamine and PGD2, in the skin most likely from mast cells by a mechanism which may be different from that of mediator release in response to antigen.

A BSTRACT Background: The relationship between the severity of atopic dermatitis (AD) and involvements of T helper (Th) 1 and Th2 cytokines has not yet been clarified yet. The aim of the present study was to understand the relationship between the severity of AD and the involvement of Th1 and Th2 cytokines. Thus, we determined cytokine production in vitro by peripheral blood mononuclear cells (PBMC) obtained from patients with AD before and after treatment. Methods: Cytokine production by PBMC obtained from patients with AD following antigen stimulation in vitro were compared before and after treatment. Enzyme-linked immunosorbent assays were used to measure cytokines. Treatment was undertaken with topical steroids and oral antihistamines. Results: Interferonγ and interleukin (IL)-12 production increased significantly after 2 weeks treatment ( P < 0.005 and P < 0.05, respectively), while IL-10 production decreased significantly after 2 and 4 weeks treatment ( P < 0.01). Granulocyte-macrophage colony stimulating factor and tumor necrosis factorα production increased significantly after treatment ( P < 0.05 and P < 0.05, respectively). The production of IL-1 β , IL-4 and IL-13 was not changed significantly. Conclusions: The T cells obtained from patients that were involved in the active inflammation of atopic dermatitis were predominately of the Th2 type and, in addition, the function of these T cells was likely to be affected by the intensity of the skin inflammation.

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