Interleukin-1 alpha enhances mast cell growth by a fibroblast-dependent mechanism

Mast cell hyperplasia is observed in various inflammatory skin diseases. Al though the pathogenesis of these conditions remains largely uninvestigated, it has been speculated that lesional mediators provide a favorable microen vironment for mast cell growth. We investigated the effect of an inflammato ry cytokine, IL-1 alpha, on mast cell growth in a mast cell/fibroblast cocu lture system. When mouse hone marrow-derived cultured mast cells (BMMC) wer e cultured on a NIH/3T3 fibroblast monolayer, IL-1 alpha. stimulated mast c ell proliferation. However, IL-1 alpha did not stimulate H-3-thymidine inco rporation in BMMC in the absence of fibroblasts. Separation of BMMC from fi broblasts by a permeable micropore membrane reduced the effect of IL-1 alph a. When BMMC were prepared from W/W-nu mice, which lack a functional c-kit, or when NIH/3T3 fibroblasts were substituted with Sl/Sl(d)-derived fibrobl asts, which lack membrane-bound stem cell factor (SCF), a lower, but signif icant, effect of IL-1 alpha was observed. Flow cytometric analysis revealed no enhancement of SCF expression on fibroblasts following stimulation with IL-1 alpha. Neutralizing antibodies against IL-3, IL-4, IL-10, and nerve g rowth factor (NGF) showed no inhibition. On the other hand, indomethacin in hibited the effect of IL-1 alpha, and prostaglandin E-2 induced mast cell g rowth in the co-cultures. These results indicate that IL-1 alpha stimulates mast cell growth by a fibroblast-dependent mechanism, in which SCF/c-kit i nteraction may participate in a major way. The mast cell growth activity in duced by this cytokine can, at least in part, be attributed to prostaglandi ns. Inflammatory cytokines may thus contribute to mast cell hyperplasia in skin diseases.