Interleukin-4 induces a switch of human intestinal mast cells from proinflammatory cells to Th2-type cells

During the last years, mast cells have been recognized as a potent cellular source of multiple cytokines. However, little is known about the regulation of cytokine production by mature human mast cells derived from mucosal sites.

Human mast cells were isolated from intestinal mucosa and cultured for 14 days in the presence of stem cell factor (SCF) alone or in combination with IL-4. Mast cells were then stimulated by IgE receptor cross-linking or bacterial infection and cytokine production was examined by RT-PCR and ELISA.

We found that human intestinal mast cells produce proinflammatory cytokines such as TNF-alpha, IL-1beta and IL-6 without further stimulation. Stimulation of the cells with gram-negative bacteria (Escherichia coli and others) caused an upregulation of TNF-alpha expression. Following IgE receptor cross-linking, we found additional expression of the Th2 cytokines IL-3, IL-5 and IL-13. Interestingly, mRNA for IL-3, IL-5 and IL-13 was also expressed in unstimulated mast cells provided they were cultured in the presence of SCF and IL-4. Moreover, IL-4 rendered mast cells capable of releasing IL-5 in response to bacterial challenge.

In the presence of the mast cell survival factor SCF, mature human mast cells produce predominantly proinflammatory cytokines, whereas in the presence of SCF and IL-4, mast cells produce not only proinflammatory but also Th2 cytokines.