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.
Fantuzzi
G
G
Department of Medicine, University of Colorado Health Sciences Center, Denver 80262, USA.
Dinarello
C A
CA
D000818:Animals; D001202:Ascitic Fluid / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D001835:Body Weight / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D016207:Cytokines / Q000097:blood* / Q000187:drug effects / Q000235:genetics; D004195:Disease Models, Animal; D005260:Female; D007003:Hypoglycemia / Q000139:chemically induced / Q000503:physiopathology; D007249:Inflammation / Q000097:blood / Q000139:chemically induced / Q000503:physiopathology*; D007509:Irritants / Q000008:administration & dosage; D051379:Mice; D008817:Mice, Mutant Strains; D010529:Peritoneal Cavity / Q000166:cytology / Q000502:physiology; D010538:Peritonitis / Q000097:blood / Q000139:chemically induced / Q000503:physiopathology; D019089:Stem Cell Factor / Q000235:genetics / Q000502:physiology*; D014425:Turpentine / Q000008:administration & dosage; D015431:Weight Loss / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D015054:Zymosan / Q000008:administration & dosage
D016207:Cytokines; D007509:Irritants; D019089:Stem Cell Factor; D015054:Zymosan; D014425:Turpentine