Effects of Chronic Treatment

We treated genetically mast cell-deficient WCB6F1 Sl/Sld mice and the congenic normal (WCB6F,-+/+) mice with the c-kit ligand recombinant rat stem cell factor" (rrSCF'"; 100 ,ug/kg per d, subcutaneously) or with vehicle for 21 d, then passively sensitized the mice with anti-dinitrophenol3 40 immunoglobulin E (IgE) antibodies, and 1 d later measured the changes in heart rate, pulmonary dynamic compliance, and pulmonary conductance, and assessed the death rates associated with intravenous challenge of these animals with specific antigen. rrSCF 4 treatment induced the development of mast cells in SI/Sid mice, and these mice exhibited tachycardia, but not death, after challenge with IgE and antigen. rrSCF'" treatment induced mast cell hyperplasia in +/+ mice, but the cardiopulmonary changes associated with passive anaphylaxis in these mice were virtually indistinguishable from those observed in control +/+ mice treated with vehicle instead of rrSCF'". Moreover, the highest dose of antigen challenge produced significantly fewer fatalities in rrSCF'`-treated than in vehicletreated +/+ mice (1/11 vs. 8/11, respectively, P < 0.01). Thus, in normal mice, chronic treatment with rrSCF " induces mast cell hyperplasia but does not increase, and in certain respects diminishes, the severity of IgE-dependent anaphylactic reactions. (J. Clin. Invest. 1993. 92:1639-1649.)