Stem cell factor-deficient mice have a dysregulation of cytokine production during local inflammation.

We have studied the responses of stem cell factor-deficient (SCF-) mice in two models of local inflammation, turpentine-induced tissue damage and zymosan-induced peritonitis. These mice have a profound mast cells deficiency. Following administration of either zymosan or turpentine, SCF- mice developed a more severe body weight loss than wild type (SCF+) mice. An exaggerated systemic production of interleukin-1beta (IL-1beta) and IL-6 was observed in SCF- mice. However, systemic tumor necrosis factor-alpha (TNF-alpha) levels were undetectable in SCF- mice following zymosan administration. The peritoneal lavage fluid (PLF) of SCF- mice also showed a marked increase in IL-1beta following zymosan administration, whereas local IL-6 and TNF-alpha production were not affected. In addition, PLF levels for the chemokine MIP-1alpha were strongly reduced in SCF- mice. This was associated with a reduced number of infiltrating cells. A possible mechanism for these differences was a reduction in IL-4 production in SCF- mice. Both local and systemic levels for IL-4 were significantly lower in SCF- mice following either zymosan or turpentine administration. Our results suggest that mast cells and/or SCF are important regulators of the production of cytokines in the course of inflammatory responses.