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-) mic e in two models of local inflammation, turpentine-induced tissue damag e and zymosan-induced peritonitis. These mice have a profound mast cel ls deficiency. Following administration of either zymosan or turpentin e, SCF mice developed a more severe body weight loss than wild type (S CF+) mice. An exagerated systemic production of interleukin-1 beta (IL -1 beta) and IL-6 was observed in SCF- mice. However, systemic tumor n ecrosis factor-alpha (TNF-alpha) levels were undetectable in SCF- mice following zymosan administration. The peritoneal lavage fluid (PLF) o f SCF- mice also showed a marked increase in IL-1 beta following zymos an administration, whereas local IL-6 and TNF-alpha production were no t affected. In addition, PLF levels for the chemokine MIP-1 alpha were strongly reduced in SCF mice. This was associated with a reduced numb er of infiltrating cells. A possible mechanism for these differences w as a reduction in IL-4 production in SCF- mice. Both local and systemi c levels for IL-4 were significantly lower in SCF mice following eithe r zymosan or turpentine administration. Our results suggest that mast cells and/or SCF are important regulators of the production of cytokin es in the course of inflammatory responses.