Effects of CI-949, a novel antiallergy compound, on host resistance in mice.
The effect of CI-949, a novel inhibitor of allergic mediator release, on immune function was assessed with holistic mouse models of immunocompetence. Resistance to the bacterial pathogens Listeria monocytogenes and Streptococcus pneumoniae and the B16F10 melanoma cell line was used to evaluate the potential of CI-949 to affect immune function. CI-949 treatment of female B6C3F1 mice increased pulmonary tumor burden at 100 mg/kg/day in the B16F10 melanoma model, with a no effect level of at least 50 mg/kg/day. A correlation was seen between decreased clearance of the B16F10 cells and increased tumor burden. However, CI-949 produced this effect only at the maximum tolerated dose. No effect of the drug was seen in the S. pneumoniae model. Host resistance to L. monocytogenes was increased after CI-949 administration, with the no adverse effect level in this model being at least equivalent to the top dose of 100 mg/kg/day. Therefore, the immune system does not appear to be adversely affected or to be a specific target for CI-949 even at an overtly toxic dose.
Bleavins
M R
MR
Parke-Davis Pharmaceutical Research, Warner-Lambert Company, Ann Arbor, Michigan 48105.
Martin
R A
RA
de la Iglesia
F A
FA
Munson
A E
AE
McCay
J A
JA
Fouant
M M
MM
White
K L
KL
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D004273:DNA, Neoplasm / Q000096:biosynthesis; D006633:Histamine Antagonists / Q000494:pharmacology*; D007109:Immunity / Q000187:drug effects*; D007211:Indoles / Q000494:pharmacology*; D007694:Killer Cells, Natural / Q000187:drug effects / Q000276:immunology; D008088:Listeriosis / Q000276:immunology; D008175:Lung Neoplasms / Q000276:immunology; D008264:Macrophages / Q000187:drug effects / Q000276:immunology; D008546:Melanoma, Experimental / Q000276:immunology; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D011008:Pneumococcal Infections / Q000276:immunology; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D013777:Tetrazoles / Q000494:pharmacology*
D004273:DNA, Neoplasm; D006633:Histamine Antagonists; D007211:Indoles; D013777:Tetrazoles; C061320:CI 949