In activated mast cells, IL-1 up-regulates the production of several Th2-related cytokines including IL-9

Mast cells can play detrimental roles in the pathophysiology and mortality observed in anaphylaxis and other Th2-dominated allergic diseases. In contr ast, these cells contribute to protective host defense mechanisms against p arasitic worm infections. After IgE/Ag activation, mast cells can produce m ultiple cytokines that may enhance allergic inflammations, while a similar panel of Th2-related cytokines may support immunological strategies against parasites. Here we report that in primary mouse bone marrow-derived mast c ells activated by ionomycin or IgE/Ag, the proinflammatory mediator IL-I (a lpha or beta) up-regulated production of IL-3, IL-5. IL-6, and IL-9 as well as TNF, i.e., cytokines implicated in many inflammatory processes includin g those associated with allergies and helminthic infections. IL-1 did not i nduce significant cytokine release In the absence of ionomycin or IgE/Ag, s uggesting that Ca-dependent signaling was required. IL-l-mediated enhanceme nt of cytokine expression was confirmed at the mRNA level by Northern blot and/or RT-PCR analysis. Our study reveals a role for IL-I in the up-regulat ion of multiple mast cell-derived cytokines, Moreover, we identify mast cel ls as a novel source of IL-9, These results are of particular Importance in the light of recent reports that strongly support a central role of IL-9 i n allergic lung inflammation and in host defense against worm infections.